近红外二区聚集诱导发光探针在生物医学中的应用 增强出版

{ "defaultlang": "zh", "titlegroup": { "articletitle": [ { "lang": "zh", "data": [ { "name": "text", "data": "近红外二区聚集诱导发光探针在生物医学中的应用" } ] }, { "lang": "en", "data": [ { "name": "text", "data": "Near-Infrared-Ⅱ AIE Probes for Biomedical Applications" } ] } ] }, "contribgroup": { "author": [ { "name": [ { "lang": "zh", "surname": "桂", "givenname": "一雄", "namestyle": "eastern", "prefix": "" }, { "lang": "en", "surname": "GUI", "givenname": "Yixiong", "namestyle": "eastern", "prefix": "" } ], "stringName": [], "aff": [ { "rid": "aff1", "text": "1" } ], "role": [ "equal", "first-author" ], "bio": [ { "lang": "zh", "text": [ "桂一雄（1997-），男，湖南永州人，硕士研究生，2020年于长沙学院获得学士学位，主要从事近红外二区聚集诱导发光材料的设计与合成的研究。 E-mail： 2070343099@email.szu.edu.cn" ], "graphic": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031637&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031649&type=", "big": 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"aff1", "text": "1" } ], "role": [], "deceased": false }, { "name": [ { "lang": "zh", "surname": "燕", "givenname": "鼎元", "namestyle": "eastern", "prefix": "" }, { "lang": "en", "surname": "YAN", "givenname": "Dingyuan", "namestyle": "eastern", "prefix": "" } ], "stringName": [], "aff": [ { "rid": "aff1", "text": "1" } ], "role": [ "corresp" ], "corresp": [ { "rid": "cor1", "lang": "en", "text": "E-mail： yandingyuan@szu.edu.cn", "data": [ { "name": "text", "data": "E-mail： yandingyuan@szu.edu.cn" } ] } ], "bio": [ { "lang": "zh", "text": [ "燕鼎元（1991-），男，山东枣庄人，博士，副研究员，2019年于南京大学获得博士学位，主要从事近红外二区新型聚集诱导发光分子材料的合成及其在光学诊疗应用中的研究。 E-mail： yandingyuan@szu.edu.cn" ], "graphic": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031668&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031678&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031673&type=", "width": "24.89202881", "height": 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"http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031684&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031696&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031691&type=", "width": "24.89202881", "height": "29.88732910", "fontsize": "" } ], "data": [ [ { "name": "text", "data": "王东" }, { "name": "text", "data": "（1985-），男，山东菏泽人，博士，特聘教授，2013年于兰州大学、2014年于法国波尔多大学获得博士学位，主要从事新型聚集诱导发光（AIE）材料的开发及其在生物成像和疾病治疗等方面应用的研究。 E-mail： " }, { "name": "text", "data": "wangd@szu.edu.cn" } ] ] } ], "email": "wangd@szu.edu.cn", "deceased": false }, { "name": [ { "lang": "zh", "surname": "唐", "givenname": "本忠", "namestyle": "eastern", "prefix": "" }, { "lang": "en", "surname": "TANG", "givenname": "Benzhong", "namestyle": "eastern", "prefix": "" } ], "stringName": [], "aff": [ { "rid": "aff2", "text": "2" } ], "role": [ "corresp" ], "corresp": [ { "rid": "cor3", "lang": "en", "text": "E-mail： tangbenz@cuhk.edu.cn", "data": [ { "name": "text", "data": "E-mail： tangbenz@cuhk.edu.cn" } ] } ], "bio": [ { "lang": "zh", "text": [ "唐本忠（1957-），男，湖北潜江人，博士，教授，中国科学院院士，亚太材料科学院院士，发展中国家科学院院士，1988年于日本京都大学获得博士学位，主要从事高分子化学和先进功能材料的研究。E-mail： tangbenz@cuhk.cuhk.edu.cn" ], "graphic": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031702&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031713&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031707&type=", "width": "24.89202499", "height": "29.88732910", "fontsize": "" } ], "data": [ [ { "name": "text", "data": "唐本忠" }, { "name": "text", "data": "（1957-），男，湖北潜江人，博士，教授，中国科学院院士，亚太材料科学院院士，发展中国家科学院院士，1988年于日本京都大学获得博士学位，主要从事高分子化学和先进功能材料的研究。E-mail： " }, { "name": "text", "data": "tangbenz@cuhk.cuhk.edu.cn" } ] ] } ], "email": "tangbenz@cuhk.cuhk.edu.cn", "deceased": false } ], "aff": [ { "id": "aff1", "intro": [ { "lang": "zh", "label": "1", "text": "深圳大学 材料学院， AIE研究中心， 广东 深圳　518000", "data": [ { "name": "text", "data": "深圳大学 材料学院， AIE研究中心， 广东 深圳　518000" } ] }, { "lang": "en", "label": "1", "text": "Center for AIE Research， College of Materials Science and Engineering， Shenzhen University， Shenzhen 518060， China", "data": [ { "name": "text", "data": "Center for AIE Research， College of Materials Science and Engineering， Shenzhen University， Shenzhen 518060， China" } ] } ] }, { "id": "aff2", "intro": [ { "lang": "zh", "label": "2", "text": "香港中文大学（深圳） 理工学院， 深圳分子聚集体科学与工程研究院， 广东 深圳　518172", "data": [ { "name": "text", "data": "香港中文大学（深圳） 理工学院， 深圳分子聚集体科学与工程研究院， 广东 深圳　518172" } ] }, { "lang": "en", "label": "2", "text": "School of Science and Engineering， Shenzhen Institute of Molecular Aggregate Science and Engineering， The Chinese University of Hong Kong， Shenzhen 518172， China", "data": [ { "name": "text", "data": "School of Science and Engineering， Shenzhen Institute of Molecular Aggregate Science and Engineering， The Chinese University of Hong Kong， Shenzhen 518172， China" } ] } ] } ] }, "abstracts": [ { "lang": "zh", "data": [ { "name": "p", "data": [ { "name": "text", "data": "近红外二区聚集诱导发光探针在生物医学中的应用是一个新兴的研究领域。近红外二区聚集诱导发光探针突破了传统荧光探针穿透深度浅、光损伤小以及聚集态荧光效率低下的限制，为深层组织的高分辨率荧光成像提供了可能。研究表明，通过合理的分子设计可实现近红外二区聚集诱导发光探针激发态能量辐射跃迁与非辐射跃迁之间的可控调节，即单一近红外二区聚集诱导发光探针可同时兼具荧光、光声和光热三模态成像能力，以及多模成像指导的光热和光动力治疗。目前，近红外二区聚集诱导发光探针已发展为构建疾病诊疗一体化平台的重要选择之一。基于此，本综述系统总结了近红外二区聚集诱导发光探针的最新研究进展，主要包括分子设计及其在生物医学中的应用。最后提出目前的发展瓶颈，并对其未来的发展方向与前景进行了展望。" } ] } ] }, { "lang": "en", "data": [ { "name": "p", "data": [ { "name": "text", "data": "The biomedical application of aggregation-induced emission（AIE） nanoprobes that emit fluorescence in the second near-infrared（NIR-Ⅱ） optical window is an emerging research area. In comparison with traditional fluorescent materials， NIR-Ⅱ AIE nanoprobes have been established to show superiority in deeper tissue penetration ability， minimized light damage， and good quantum yield in aggregated state. It has been proven that rational molecular engineering could realize the controllable regulation between the radiative and nonradiative dispersion of the excited state energy of the NIR-Ⅱ AIE chromophores. The unique propeller-like conformation of AIE luminogens determines its easily modulable attribute between radiative decay which can be used for fluorescence imaging（FLI） and nonradiative decay which can be harnessed to conduct photothermal imaging（PTI）/photoacoustic imaging（PAI）/photothermal therapy（PTT）/photodynamic therapy（PDT）. At present， AIE luminogens have developed into an alternative candidate to build integrated “one-for-all” theranostic platform. Herein， this review systematically summarizes the latest research advancements of NIR-Ⅱ AIE probes， on the aspects of molecular design and biomedical applications. Besides， the current challenges and future research directions of NIR-Ⅱ AIE nanoprobes are briefly discussed in the end." } ] } ] } ], "keyword": [ { "lang": "zh", "data": [ [ { "name": "text", "data": "近红外二区聚集诱导发光探针" } ], [ { "name": "text", "data": "生物医学应用" } ], [ { "name": "text", "data": "疾病诊疗一体化" } ] ] }, { "lang": "en", "data": [ [ { "name": "text", "data": "near-infrared-Ⅱ probes showing aggregation-induced emission characteristics" } ], [ { "name": "text", "data": "biomedical applications" } ], [ { "name": "text", "data": "disease theranostics" } ] ] } ], "highlights": [], "body": [ { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "1　引　　言" } ], "level": "1", "id": "s1" } }, { "name": "p", "data": [ { "name": "text", "data": "荧光材料已被广泛应用在光电器件、生物传感、纳米医学等领域。其中，基于荧光探针的荧光成像（FLI）因其非侵入式的可视化检测方式、实时原位、高时空分辨率等优点而被广泛应用在活体成像、临床诊断、癌症治疗等生物医学领域" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "1", "type": "bibr", "rid": "R1", "data": [ { "name": "text", "data": "1" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "2", "type": "bibr", "rid": "R2", "data": [ { "name": "text", "data": "2" } ] } } ], "rid": [ "R1", "R2" ], "text": "1-2", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。过去的几十年中开发的荧光探针发射波长主要集中在传统可见光（400~700 nm）与近红外一区窗口（NIR-Ⅰ，700~900 nm）" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "3", "type": "bibr", "rid": "R3", "data": [ { "name": "text", "data": "3" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。然而在这一波段范围下，光子的散射程度高、穿透深度差、生物组织自发荧光背景干扰大，极大地限制了荧光探针在生物医学上的应用。与可见光以及NIR-Ⅰ窗口相比，发射在1 000~1 700 nm之间的近红外二区（NIR-Ⅱ）窗口的荧光探针具有更低的光散射以及更强的生物组织穿透能力（约5~20 mm）。此外，该波段的组织自发荧光低，从而可以实现更高分辨率和更高信背比（Signal to background ratio, SBR）的FLI" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "4", "type": "bibr", "rid": "R4", "data": [ { "name": "text", "data": "4" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "6", "type": "bibr", "rid": "R6", "data": [ { "name": "text", "data": "6" } ] } } ], "rid": [ "R4", "R5", "R6" ], "text": "4-6", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "目前，已经报道了多种类型的NIR-Ⅱ荧光材料" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "7", "type": "bibr", "rid": "R7", "data": [ { "name": "text", "data": "7" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。其中，无机类荧光材料主要包含单壁碳纳米管、金纳米棒、量子点" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "8", "type": "bibr", "rid": "R8", "data": [ { "name": "text", "data": "8" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "10", "type": "bibr", "rid": "R10", "data": [ { "name": "text", "data": "10" } ] } } ], "rid": [ "R8", "R9", "R10" ], "text": "8-10", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "等，有机类荧光材料主要包括共轭聚合物和小分子染料" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "11", "type": "bibr", "rid": "R11", "data": [ { "name": "text", "data": "11" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "13", "type": "bibr", "rid": "R13", "data": [ { "name": "text", "data": "13" } ] } } ], "rid": [ "R11", "R12", "R13" ], "text": "11-13", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。无机类荧光材料因其难以被生物组织降解而引起生物相容性方面的担忧。相比之下，有机荧光探针更容易被生物体代谢，且结构和纯度确切、容易修饰加工，因而备受研究人员青睐。例如，亚甲基蓝" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "14", "type": "bibr", "rid": "R14", "data": [ { "name": "text", "data": "14" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "和吲哚菁绿（Indocyanine green，ICG）" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "15", "type": "bibr", "rid": "R15", "data": [ { "name": "text", "data": "15" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "已获美国食品药品监督管理局（Food and drug administration, FDA）批准，被广泛应用于临床研究" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "16", "type": "bibr", "rid": "R16", "data": [ { "name": "text", "data": "16" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "有机荧光分子随着共轭程度的扩展，探针分子吸收/发射红移的同时，疏水性也随之增加，在生理环境下难免会发生聚集。然而，传统的有机荧光材料在聚集或者高浓度状态下容易发生π-π堆积，从而产生聚集导致荧光猝灭（Aggregation-caused quenching，ACQ）效应，使得成像与治疗效果不尽人意" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "17", "type": "bibr", "rid": "R17", "data": [ { "name": "text", "data": "17" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "18", "type": "bibr", "rid": "R18", "data": [ { "name": "text", "data": "18" } ] } } ], "rid": [ "R17", "R18" ], "text": "17-18", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。2001年，唐本忠院士等通过六苯基噻咯发现了一种与ACQ现象完全相反的光物理现象，称之为聚集诱导发光（AIE）" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "19", "type": "bibr", "rid": "R19", "data": [ { "name": "text", "data": "19" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。如" }, { "name": "xref", "data": { "text": "图 1", "type": "fig", "rid": "F1", "data": [ { "name": "text", "data": "图 1" } ] } }, { "name": "text", "data": "（a）所示，AIE分子在分散状态时，不产生荧光或只产生很弱的荧光；当AIE分子处于聚集态时，由于分子内运动受限（Restriction of intra-/intermolecular motion, RIM）使得非辐射跃迁能量耗散途径得以抑制，从而表现出增强的荧光发射。此外，还可以通过合理设计分子结构和骨架调控激发态能量辐射耗散与非辐射耗散的平衡，实现不同性能如高荧光量子产率（Quantum yield, QY）、高活性氧（ROS）产生效率、高光热转化效率（Photothermal conversion efficiency, PCE）或者多模态诊疗等AIE探针的构建（" }, { "name": "xref", "data": { "text": "图1", "type": "fig", "rid": "F1", "data": [ { "name": "text", "data": "图1" } ] } }, { "name": "text", "data": "（b））。因此，AIE荧光探针除了其优异的FLI效果之外，在光动力治疗（PDT）与光热治疗（PTT）领域也具有广泛的应用前景，成为生物医学诊疗领域一颗冉冉升起的新星" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "19", "type": "bibr", "rid": "R19", "data": [ { "name": "text", "data": "19" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "23", "type": "bibr", "rid": "R23", "data": [ { "name": "text", "data": "23" } ] } } ], "rid": [ "R19", "R20", "R21", "R22", "R23" ], "text": "19-23", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。" } ] }, { "name": "fig", "data": { "id": "F1", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图 1" } ], "title": [ { "name": "text", "data": "（a）聚集诱导发光分子诊疗功能示意图；（b）雅布隆斯基能级图。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig. 1" } ], "title": [ { "name": "text", "data": "（a）Graphic description of the theranostic functionality of AIEgens. （b）Jablonski diagram." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031719&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031728&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031723&type=", "width": "105.81860352", "height": "66.05284882", "fontsize": "" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "兼具NIR-Ⅱ发射和AIE特征（NIR-Ⅱ AIE）的荧光探针可以增强探针在聚集状态下的荧光效率并可用于更深组织部位的成像。自2018年首次报道以来" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "24", "type": "bibr", "rid": "R24", "data": [ { "name": "text", "data": "24" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "，NIR-Ⅱ AIE荧光探针引起了越来越多的研究兴趣，基于它的生物应用也在过去几年中经历了蓬勃发展" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "25", "type": "bibr", "rid": "R25", "data": [ { "name": "text", "data": "25" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "26", "type": "bibr", "rid": "R26", "data": [ { "name": "text", "data": "26" } ] } } ], "rid": [ "R25", "R26" ], "text": "25-26", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。基于此，本文总结了NIR-Ⅱ AIE探针在生物医学应用中的最新研究进展。首先讨论了NIR-Ⅱ AIE探针在活体成像中的应用；其次概述了基于NIR-Ⅱ AIE探针的FLI和/或光声成像（PAI）用于疾病诊断；随后讨论了NIR-Ⅱ AIE探针用于疾病的诊疗一体化；最后对NIR-Ⅱ AIE探针在生物医学应用中的发展方向与前景进行了展望。" } ] } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2　活体成像" } ], "level": "1", "id": "s2" } }, { "name": "p", "data": [ { "name": "text", "data": "自2001年AIE概念提出以来，AIE荧光探针由于在聚集态具有高亮度优势，在活体成像上取得了巨大的成就，但深层组织活体成像仍受限于短波长光穿透深度较差的限制。而发射在NIR-Ⅱ窗口的光可以减少组织对光子散射，有望实现深度层组织的FLI。通过整合NIR-Ⅱ与AIE特征，开发具备聚集状态下亮度高、组织穿透能力强等优势的NIR-Ⅱ AIE荧光探针，非常适合用于深层组织活体成像。迄今为止，NIR-Ⅱ AIE探针已成功用于血管成像、器官（如肠胃、膀胱、输尿管等）成像等。" } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2.1　血管成像" } ], "level": "2", "id": "s2a" } }, { "name": "p", "data": [ { "name": "text", "data": "血管功能与许多病理过程息息相关，包括肿瘤的生成与转移、外周动脉疾病以及心脑血管疾病等" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "27", "type": "bibr", "rid": "R27", "data": [ { "name": "text", "data": "27" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "29", "type": "bibr", "rid": "R29", "data": [ { "name": "text", "data": "29" } ] } } ], "rid": [ "R27", "R28", "R29" ], "text": "27-29", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。血管造影剂被认为是评估血管功能不可或缺的工具，虽然经过几十年的发展，但仍缺乏对血管精细结构和深层分布血管进行高灵敏成像的造影剂。随着NIR-Ⅱ AIE探针的快速发展，更多性能优异的血管造影剂得以开发。" }, { "name": "xref", "data": { "text": "图2", "type": "fig", "rid": "F2", "data": [ { "name": "text", "data": "图2" } ] } }, { "name": "text", "data": "（a）所示为近些年报道的用于深部精细血管成像的NIR-Ⅱ AIE分子，如AQMN-3" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "30", "type": "bibr", "rid": "R30", "data": [ { "name": "text", "data": "30" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、TTB" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "31", "type": "bibr", "rid": "R31", "data": [ { "name": "text", "data": "31" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "32", "type": "bibr", "rid": "R32", "data": [ { "name": "text", "data": "32" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、OTPA-BBT" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "33", "type": "bibr", "rid": "R33", "data": [ { "name": "text", "data": "33" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、TBP-" }, { "name": "italic", "data": [ { "name": "text", "data": "b" } ] }, { "name": "text", "data": "-DFA" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "34", "type": "bibr", "rid": "R34", "data": [ { "name": "text", "data": "34" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、BPST" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "35", "type": "bibr", "rid": "R35", "data": [ { "name": "text", "data": "35" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、TQ-BPN" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "36", "type": "bibr", "rid": "R36", "data": [ { "name": "text", "data": "36" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、BPN-BBT" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "37", "type": "bibr", "rid": "R37", "data": [ { "name": "text", "data": "37" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、TB1" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "38", "type": "bibr", "rid": "R38", "data": [ { "name": "text", "data": "38" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "等。血管功能评估的准确性取决于成像的分辨率与灵敏度，而这两者主要由荧光探针的亮度决定。研究表明，荧光探针的亮度主要是由摩尔消光系数（Molar extinction coefficient，MEC）与QY共同决定。获得较高MEC最有效的策略是构建平面型长共轭骨架" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "39", "type": "bibr", "rid": "R39", "data": [ { "name": "text", "data": "39" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "，然而传统这种构型的分子在聚集态下容易发生ACQ现象，降低QY。而AIE探针能提高探针聚集态的QY，但是AIE固有的扭曲结构会破坏共轭程度，导致MEC降低。因此，实现这两种策略的有机结合将为构建高亮度荧光探针提供新思路。" } ] }, { "name": "fig", "data": { "id": "F2", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图2" } ], "title": [ { "name": "text", "data": "（a）用于血管成像的代表性NIR-Ⅱ AIE分子结构式；（b）TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB的荧光发射光谱；（c）TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB的AIE曲线；（d）TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs制备示意图；（e）脑血管显微成像系统示意图；（f）TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs用于脑血管的NIR-Ⅱb FLI；（g）图（f）中绿色虚线截面的荧光强度的高斯分布图；（h）TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs用于小鼠股骨血管NIR-Ⅱ FLI" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "32", "type": "bibr", "rid": "R32", "data": [ { "name": "text", "data": "32" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.2" } ], "title": [ { "name": "text", "data": "（a）Chemical structures of representative NIR-Ⅱ AIE molecules for vascular imaging. （b）PL spectra of TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB. （c）AIE curve of TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB. （d）Schematic illustration of the preparation of TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs. （e）Schematic illustration of cerebrovascular microscopic imaging. （f）TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs for NIR-Ⅱb fluorescence imaging of the cerebral vasculature in living mice.（g）The cross-sectional fluorescence intensity profile fitted with Gaussian along green-dashed lines in Fig.（f）. （h）TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs for NIR-Ⅱ fluorescence imaging of femoral vessels in living mice" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "32", "type": "bibr", "rid": "R32", "data": [ { "name": "text", "data": "32" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031735&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031744&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031740&type=", "width": "163.34408569", "height": "141.09130859", "fontsize": "" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "对此，2020年，唐本忠院士团队提出一种分子设计策略：通过将平面基元二噻吩并[3,2-" }, { "name": "italic", "data": [ { "name": "text", "data": "b" } ] }, { "name": "text", "data": ":2′,3′-" }, { "name": "italic", "data": [ { "name": "text", "data": "d" } ] }, { "name": "text", "data": "]噻吩引入到扭曲骨架中，同时提高MEC（2.07 × 10" }, { "name": "sup", "data": [ { "name": "text", "data": "4" } ] }, { "name": "text", "data": " L·mol" }, { "name": "sup", "data": [ { "name": "text", "data": "-1" } ] }, { "name": "text", "data": "·cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-1" } ] }, { "name": "text", "data": "）与聚集态QY（0.031%），实现高亮度探针TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB的设计合成" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "32", "type": "bibr", "rid": "R32", "data": [ { "name": "text", "data": "32" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。如" }, { "name": "xref", "data": { "text": "图2", "type": "fig", "rid": "F2", "data": [ { "name": "text", "data": "图2" } ] } }, { "name": "text", "data": "（b）所示，TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB的最大发射为1 060 nm，尾部可以延伸至成像效果更佳的近红外Ⅱb（NIR-Ⅱb， 1 500~1 700 nm）窗口，且在聚集状态表现出明显的AIE特性（" }, { "name": "xref", "data": { "text": "图2", "type": "fig", "rid": "F2", "data": [ { "name": "text", "data": "图2" } ] } }, { "name": "text", "data": "（c））。为了更好地研究探针在生物体内的应用，作者将TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB使用FDA批准的表面活性剂Pluronic F127封装成水溶性优异的 纳米粒子（NPs）TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs（" }, { "name": "xref", "data": { "text": "图2", "type": "fig", "rid": "F2", "data": [ { "name": "text", "data": "图2" } ] } }, { "name": "text", "data": "（d））" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "32", "type": "bibr", "rid": "R32", "data": [ { "name": "text", "data": "32" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。如" }, { "name": "xref", "data": { "text": "图 2", "type": "fig", "rid": "F2", "data": [ { "name": "text", "data": "图 2" } ] } }, { "name": "text", "data": "（e）所示，通过尾部静脉注射TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs（100 μL, 2.5 mg·mL" }, { "name": "sup", "data": [ { "name": "text", "data": "-1" } ] }, { "name": "text", "data": "），使用793 nm激发光源对小鼠脑血管系统进行高倍颅骨FLI，可以清晰地显示直径最小3.3 μm的脑血管，且SBR高达6.3（" }, { "name": "xref", "data": { "text": "图 2", "type": "fig", "rid": "F2", "data": [ { "name": "text", "data": "图 2" } ] } }, { "name": "text", "data": "（f）、（g））。同时TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs也适用于其他部位的血管成像，如小腿后肢血管成像等（" }, { "name": "xref", "data": { "text": "图2", "type": "fig", "rid": "F2", "data": [ { "name": "text", "data": "图2" } ] } }, { "name": "text", "data": "（h））。鉴于TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB具有在NIR-Ⅱb生物窗口成像以及高亮度两方面的优势，TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs有望实现对深层分布血管的高分辨率成像，并为开发高亮度NIR-Ⅱ荧光探针提供一种全新的设计策略。" } ] } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2.2　器官成像" } ], "level": "2", "id": "s2b" } }, { "name": "p", "data": [ { "name": "text", "data": "器官的高分辨成像可以更好地服务于临床医学诊断。基于NIR-Ⅱ AIE荧光探针可以实现对胃肠道（Gastrointestinal, GI）" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "40", "type": "bibr", "rid": "R40", "data": [ { "name": "text", "data": "40" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、膀胱" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "32", "type": "bibr", "rid": "R32", "data": [ { "name": "text", "data": "32" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、输尿管" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "41", "type": "bibr", "rid": "R41", "data": [ { "name": "text", "data": "41" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "等器官的FLI。对于胃肠道微环境的实时监测有助于了解消化系统疾病，且胃肠道组织的病变还与多种疾病有关，如糖尿病、甲状腺疾病和结直肠癌等" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "42", "type": "bibr", "rid": "R42", "data": [ { "name": "text", "data": "42" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。Hong等首次设计并合成了用于体内生物医学成像的近红外有机AIE荧光点（HLZ-BTED）" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "43", "type": "bibr", "rid": "R43", "data": [ { "name": "text", "data": "43" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "，并且首次利用AIE探针对患者的胃肠道进行了非侵入性和实时NIR-Ⅱ成像。通过观察GI蠕动的健康状态评估肠道运动功能障碍，以及评估药物对肠梗阻的影响。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "2020年，Tang等开发的NIR-Ⅱ AIE探针（BPN-BBT）在1 400 nm处仍有较强的荧光发射（" }, { "name": "xref", "data": { "text": "图 3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "图 3" } ] } }, { "name": "text", "data": "（a）、（b）），首次实现了基于AIE探针的多种器官的NIR-Ⅱ FLI" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "37", "type": "bibr", "rid": "R37", "data": [ { "name": "text", "data": "37" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。通过喂食老鼠少量的BPN-BBT纳米点（0.1 mmol·L" }, { "name": "sup", "data": [ { "name": "text", "data": "-1" } ] }, { "name": "text", "data": "，0.2 mL），然后在不同时间节点使用NIR-Ⅱ FLI系统成像。如" }, { "name": "xref", "data": { "text": "图3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "图3" } ] } }, { "name": "text", "data": "（c）所示，AIE纳米点荧光信号初始SBR值高达50。随着时间的推移，荧光信号从胃部（10 min）移动到十二指肠（30~60 min），然后是小肠（2~5 h），最后是大肠（5 h），清楚地显示了食物在消化系统中的移动过程。实现了深度大于7 mm的胃肠道高分辨率实时监测，为消化系统疾病的精确诊断提供了可能。" } ] }, { "name": "fig", "data": { "id": "F3", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图３" } ], "title": [ { "name": "text", "data": "（a）BPN-BBT的分子结构式；（b）BPN-BBT点的吸收和发射光谱；（c）用BPN-BBT点灌胃的大鼠在不同时间点的胃肠道NIR-Ⅱ FLI（左）以及相对应的信背比（右）" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "37", "type": "bibr", "rid": "R37", "data": [ { "name": "text", "data": "37" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "；（d）BBTD的分子结构式；（e）BBTD在THF和THF/甲醇（1/9）中的荧光光谱；（f）血液环境下BBTD点48 h内不同时间点的荧光图像（左）及相应的荧光强度（右）；（g）不同时间和角度下小鼠全身FLI图；（h）注射BBTD点48 h后小鼠主要脏器的荧光分布图" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "44", "type": "bibr", "rid": "R44", "data": [ { "name": "text", "data": "44" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.3" } ], "title": [ { "name": "text", "data": "（a）Molecular structure of BPN-BBT.（b）Absorption and emission spectra of BPN-BBT dots.（c）" }, { "name": "italic", "data": [ { "name": "text", "data": "In vivo" } ] }, { "name": "text", "data": " NIR-II fluorescence images and corresponding SBR of the GI tract of the rat gavaged with BPN-BBT dots at various time points" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "37", "type": "bibr", "rid": "R37", "data": [ { "name": "text", "data": "37" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": ".（d）Molecular structure of BBTD.（e）Fluorescence spectra of BBTD in THF and THF/methanol mixture（1/9）.（f）Fluorescence images of BBTD Pdots in blood environment at different time points（left） and the corresponding fluorescence intensity during in 48 h（right）.（g）" }, { "name": "italic", "data": [ { "name": "text", "data": "In vivo" } ] }, { "name": "text", "data": " fluorescence imaging of whole-body at different imaging view.（h）Biodistribution of main organs of BBTD Pdots-treated mice after 48 h post-injection" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "44", "type": "bibr", "rid": "R44", "data": [ { "name": "text", "data": "44" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031749&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031761&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031756&type=", "width": "164.26184082", "height": "69.29296875", "fontsize": "" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "同年，Li等开发的超亮NIR-Ⅱ发射聚合物点（Polymer dots, Pdots）由AIE分子BBTD和两亲性聚合物PS-PEG构成（" }, { "name": "xref", "data": { "text": "图3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "图3" } ] } }, { "name": "text", "data": "（d））" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "44", "type": "bibr", "rid": "R44", "data": [ { "name": "text", "data": "44" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。如" }, { "name": "xref", "data": { "text": "图3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "图3" } ] } }, { "name": "text", "data": "（e）所示，BBTD在固态下的亮度明显高于其THF溶液，表明其优异的AIE特性。此外，BBTD Pdots在血液中24 h后仍能保持较亮的荧光信号，可用于长期示踪（" }, { "name": "xref", "data": { "text": "图3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "图3" } ] } }, { "name": "text", "data": "（f））。利用NIR-Ⅱ Pdots的长血液循环和高亮度特点，通过NIR-Ⅱ FLI可以清楚地观察到小鼠肝、脾、肺和肾等深层组织的脏器（" }, { "name": "xref", "data": { "text": "图3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "图3" } ] } }, { "name": "text", "data": "（g）、" } ] }, { "name": "p", "data": [ { "name": "text", "data": "（h））。" } ] } ] } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "3　疾病诊断" } ], "level": "1", "id": "s3" } }, { "name": "p", "data": [ { "name": "text", "data": "疾病的早期诊断对最终治疗效果起到至关重要的作用" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "45", "type": "bibr", "rid": "R45", "data": [ { "name": "text", "data": "45" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。传统的成像技术，如计算机断层扫描(Computed tomography, CT)、磁共振成像（Magnetic resonance imaging, MRI）和超声（Ultrasound, US），已广泛用于疾病的临床诊断以及治疗后的影像学评估。但强电离辐射和有限的空间分辨率极大地限制了对疾病的精准诊断。与传统的成像诊断技术相比，NIR-Ⅱ FLI体现出优异的成像分辨率和诊断准确性、极低的生物毒性以及不受应用场景限制的优势，因此得到生物医学研究者的青睐" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "26", "type": "bibr", "rid": "R26", "data": [ { "name": "text", "data": "26" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。PAI作为另一种光学诊断方案，能够提供具有厘米级深度的成像，并可以微观空间分辨率描绘深部肿瘤轮廓。然而，单一模态的PAI仍面临成像灵敏度不够等缺点" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "46", "type": "bibr", "rid": "R46", "data": [ { "name": "text", "data": "46" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。基于此，有机结合FLI与PAI的优点，可以相互取长补短，实现对深层组织疾病的高灵敏度、高空间分辨率成像，大大提高疾病的临床诊断效率。" } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "3.1　肿瘤诊断" } ], "level": "2", "id": "s3a" } }, { "name": "p", "data": [ { "name": "text", "data": "在临床外科肿瘤学中，精准鉴别肿瘤的成像技术对手术切除肿瘤结节具有重要的作用。成像的精度和效果与荧光探针的亮度密切相关。基于此，Tang等开发了一种具有高亮度的pH响应性纳米探针pNIR-4，能够特异性地富集在肿瘤部位，为肿瘤的精准诊断提供可能" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "47", "type": "bibr", "rid": "R47", "data": [ { "name": "text", "data": "47" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。聚合物pNIR-4中的平面性噻吩单元可以提高探针的MEC (5.73×10" }, { "name": "sup", "data": [ { "name": "text", "data": "3" } ] }, { "name": "text", "data": " L·mol" }, { "name": "sup", "data": [ { "name": "text", "data": "-1" } ] }, { "name": "text", "data": "·cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-1" } ] }, { "name": "text", "data": ")，而扭曲的噻吩衍生物可以增大分子空间位阻，避免分子间强π-π相互作用，提高聚集态下的QY(2.24%)，从而保证了荧光探针整体较高的亮度。为了克服纳米探针在肿瘤处难以积聚的难题，如" }, { "name": "xref", "data": { "text": "图4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "图4" } ] } }, { "name": "text", "data": "（a）所示，使用pH响应性共聚物PCL-b-PAE和PCL-b-PEG作为混合基质来封装pNIR-4，形成pNIR4-PAE NPs。该纳米粒子在血液环境中（pH=7.4），PAE链由于去质子化而坍塌到壳的内部，使PEG暴露在pNIR4-PAE纳米粒表面，可以延长血液循环时间。当纳米粒子经过被动运输到达肿瘤部位时，偏酸性的肿瘤微环境（pH=6.5~6.8）触发了PAE的质子化，导致正电荷的PAE在纳米粒表面暴露，提高pNIR4-PAE NPs在肿瘤部位的积累和细胞摄取，解决了腹膜癌术前评估和术中影像学观察的难题。将pNIR4-PAE NPs静脉注射到4T1肿瘤小鼠内，24 h后纳米探针的NIR-Ⅱ荧光和荧光素酶的生物发光信号在腹膜腔内可以很好地重叠（" }, { "name": "xref", "data": { "text": "图4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "图4" } ] } }, { "name": "text", "data": "（b）），表明纳米探针可以准确地定位肿瘤的位置。尽管外科医生可以在无成像手段导航下手术切除直径较大（" }, { "name": "text", "data": ">" }, { "name": "text", "data": "1 mm）的肿瘤，但仍有许多微小肿瘤结节难以识别和切除，容易引起癌症的复发。而通过在pNIR4-PAE NPs NIR-Ⅱ FLI引导下进行第二轮手术，可以切除掉更多的亚毫米大小的微小肿瘤（" }, { "name": "xref", "data": { "text": "图4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "图4" } ] } }, { "name": "text", "data": "（c）~（d）），大大降低肿瘤后期复发的风险。据估计，近90%的癌症致死是由肿瘤转移引起的。而转移的肿瘤为诊断以及治疗造成了很大的困难，主要原因是转移性肿瘤体积小、组织学形态无特异性，且血管分布较少而造成高通透性和滞留效应(Enhanced permeability and retention effect, EPR)减弱，导致手术过程中难以发现和彻底切除" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "48", "type": "bibr", "rid": "R48", "data": [ { "name": "text", "data": "48" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "49", "type": "bibr", "rid": "R49", "data": [ { "name": "text", "data": "49" } ] } } ], "rid": [ "R48", "R49" ], "text": "48-49", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。基于此，Li等开发了一个具有特异性肿瘤靶向功能的NIR-Ⅱ Pdots" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "44", "type": "bibr", "rid": "R44", "data": [ { "name": "text", "data": "44" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。如" }, { "name": "xref", "data": { "text": "图4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "图4" } ] } }, { "name": "text", "data": "（e）所示，通过将促性腺激素释放激素（Gonadotropin-releasing hormone, GnRH）共价连接到NIR-Ⅱ Pdots上构建NIR-Ⅱ Pdots-GnRH。所得到的复合纳米探针可以通过靶向卵巢癌细胞中过表达的GnRH受体，增强对肿瘤细胞的亲和力，有效地聚集到转移性肿瘤区域，最终实现对转移性卵巢癌肿瘤的实时监测。将NIR-Ⅱ Pdots-GnRH以4 mg/kg的剂量静脉注射到腹膜转移瘤的荷瘤小鼠体内，48 h后进行NIR-Ⅱ FLI，如" }, { "name": "xref", "data": { "text": "图4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "图4" } ] } }, { "name": "text", "data": "（f）所示，NIR-Ⅱ FLI可以清楚地勾勒出肿瘤边界，肿瘤间质区域的肿瘤与正常组织的信噪比（" }, { "name": "italic", "data": [ { "name": "text", "data": "T" } ] }, { "name": "text", "data": "/" }, { "name": "italic", "data": [ { "name": "text", "data": "N" } ] }, { "name": "text", "data": "）值高达5.5，因此能够轻易地在NIR-Ⅱ FLI引导下识别和彻底切除发生转移的微小尺寸（～2 mm）的肿瘤。此外，在淋巴转移瘤小鼠模型中，通过静脉注射NIR-Ⅱ Pdots-GnRH探针，所有淋巴转移灶（1、3和11）比正常淋巴结显示出更高的平均荧光强度，从而更有效地检测淋巴转移瘤（" }, { "name": "xref", "data": { "text": "图4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "图4" } ] } }, { "name": "text", "data": "（g））。因此，基于AIE探针的NIR-Ⅱ FLI在诊断与手术导航方面展现出巨大的临床应用潜力" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "50", "type": "bibr", "rid": "R50", "data": [ { "name": "text", "data": "50" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。" } ] }, { "name": "fig", "data": { "id": "F4", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图4" } ], "title": [ { "name": "text", "data": "（a）pNIR4-PAE NPs制备示意图；（b）肿瘤切除前后腹腔的生物发光和NIR-Ⅱ FLI图；（c）未导航组和pNIR4-PAE NPs导航组所切除肿瘤结节的生物发光和NIR-Ⅱ FLI图；（d）切除结节直径统计数据" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "47", "type": "bibr", "rid": "R47", "data": [ { "name": "text", "data": "47" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "；（e）NIR-Ⅱ Pdots-GnRH NPs制备示意图及其在体内转移性卵巢癌检测中的应用示意图；（f）人卵巢癌腹膜转移模型在第48 h的NIR-Ⅱ FLI以及肿瘤标记处放大图；（g）卵巢淋巴转移模型注射NIR-Ⅱ Pdots-GnRH NPs后第48 h的NIR-Ⅱ FLI图（左）、切除淋巴结组织（No.1~No.11）的明场照片（中）和NIR-Ⅱ FLI图（右）" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "44", "type": "bibr", "rid": "R44", "data": [ { "name": "text", "data": "44" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.4" } ], "title": [ { "name": "text", "data": "（a）Schematic illustration of the fabrication of pNIR4-PAE NPs. （b）Bioluminescence and NIR-Ⅱ imaging of the abdominal cavity before and after tumor resection. （c）Bioluminescence and NIR-Ⅱ imaging of resected nodules of unguided and pNIR4-PAE NPs-guided groups. （d）Statistical data of nodule diameters resected. （e）Schematic illustration of the preparation of tumor targeted NIR-Ⅱ Pdots-GnRH NPs and their applications of " }, { "name": "italic", "data": [ { "name": "text", "data": "in vivo" } ] }, { "name": "text", "data": " metastatic ovarian cancer detection. （f）NIR-Ⅱ fluorescence imaging of human ovarian cancer peritoneal metastasis model at 48 h and magnification at tumor markers. （g）NIR-Ⅱ fluorescence images of ovarian lymphatic metastases mode obtained at 48 h（left）， the optical photos（medium） and NIR-Ⅱ fluorescence images of the resected lymph node tissues（No.1-No.11） " }, { "name": "italic", "data": [ { "name": "text", "data": "in vitro" } ] }, { "name": "text", "data": "（right）" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "44", "type": "bibr", "rid": "R44", "data": [ { "name": "text", "data": "44" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031767&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031780&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031772&type=", "width": "164.20379639", "height": "92.71582031", "fontsize": "" } ] } } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "3.2　炎症诊断" } ], "level": "2", "id": "s3b" } }, { "name": "p", "data": [ { "name": "text", "data": "炎症是许多重大疾病的先兆，如糖尿病、癌症和心脏病等" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "51", "type": "bibr", "rid": "R51", "data": [ { "name": "text", "data": "51" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。据调查，慢性炎症可能会诱导癌症的发生，并为肿瘤的发展提供动力。因此，炎症的非侵入式特异性检测对于疾病早期临床诊断至关重要。2021年，Tian等使用NIR-Ⅱ FLI辅助诊断炎症性肠病（Inflammatory bowel disease, IBD）" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "52", "type": "bibr", "rid": "R52", "data": [ { "name": "text", "data": "52" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。在IBD小鼠模型中，他们通过近红外探针检测偶氮还原酶活性，成功地显示了发生炎症的肠道。此外，在炎症病灶处，机体产生的大量H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "等ROS使得氧化应激加剧，从而导致组织损伤和炎症加剧。因此内源性H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "也可以作为炎症诊断的生物标志物之一，可通过对于H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "特异性响应的NIR-Ⅱ探针来实现炎症部位的定位和诊断。多光谱光声断层扫描（Multispectral optoacoustic tomograph, MSOT）是一种新兴的成像方式，它通过收集由光激发纳米粒子产生的超声波，从而达到具有高分辨率和深穿透能力的成像效果。基于此，Zhao等开发了一种激活型双模态成像（FLI/MSOT）NIR-Ⅱ AIE纳米探针" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "53", "type": "bibr", "rid": "R53", "data": [ { "name": "text", "data": "53" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。如" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "（a）所示，BTPE-NO" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "中硝基苯氧乙酰胺基团不仅可识别生物标记物 H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "，还可作为发光猝灭基团。当BTPE-NO" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "与炎症部位过表达的H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "反应后，生成BTPE-NH" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "，产生明亮的NIR-Ⅱ荧光发射和光声信号，从而实现对炎症部位的双模态成像。通过使用Pluronic F127包裹BTPE-NO" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "分子，制备成纳米探针BTPE-NO" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "@F127，成功地实现了曲唑酮诱导的小鼠肝损伤检测。在注射BTPE-NO2@F127 120 min后，荧光强度随着曲唑酮剂量的增加而显著增强（" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "（b））。使用3D MSOT成像可进一步准确定位小鼠肝损伤病灶部位，且随着曲唑酮剂量的提高，识别响应后BTPE-NH" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "产生的光声信号强度也随之增大（" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "（c））。" } ] }, { "name": "fig", "data": { "id": "F5", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图5" } ], "title": [ { "name": "text", "data": "（a）纳米探针BTPE-NO" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "@F127制备示意图及其应用；（b）对照组及BTPE-NO" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "@F127组活体小鼠肝炎位置的NIR-Ⅱ FLI图；（c）BTPE-NO" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "@F127纳米探针在肝炎小鼠体内的3D MSOT成像" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "53", "type": "bibr", "rid": "R53", "data": [ { "name": "text", "data": "53" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "；（d）通过“环稠化”策略构建NIR-Ⅱ区发射分子结构和设计示意图；（e）TTQP NPs和TTQ-DP NPs的吸收和发射光谱；（f）TTQP NPs和TTQ-DP NPs的AIE曲线；（g）TTQP NPs和TTQ-DP NPs在水中的荧光亮度；（h）TTQP NPs灌胃后不同时间点的体内NIR-Ⅱ FLI图；（i）小鼠去除腹部皮肤后肠道FLI；PBS和LPS处理小鼠离体胃、肠的明场（j）和NIR-Ⅱ FLI（k）图" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "54", "type": "bibr", "rid": "R54", "data": [ { "name": "text", "data": "54" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.5" } ], "title": [ { "name": "text", "data": "（a）Schematic representation for the fabrication of nanoprobe BTPE-NO" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "@F127 and its applications. （b）NIR-Ⅱ fluorescence imaging of hepatitis location in control group and BTPE-NO2@F127 group of live mice. （c）3D MSOT imaging of BTPE-NO2@F127 nanoprobe in hepatitis mice " }, { "name": "italic", "data": [ { "name": "text", "data": "in vivo" } ] }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "53", "type": "bibr", "rid": "R53", "data": [ { "name": "text", "data": "53" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": ". （d）Schematic illustration of the structure and design of the emission molecule in the NIR-Ⅱ constructed by the “ring-fusion” strategy. （e）Absorption and PL spectra of TTQP and TTQ-DP NPs. （f）AIE curves for TTQP and TTQ-DP. （g）The fluorescence brightness of TTQP and TTQ-DP NPs in water.（h）Representative " }, { "name": "italic", "data": [ { "name": "text", "data": "in vivo" } ] }, { "name": "text", "data": " NIR-Ⅱ fluorescence images at different time points post gavage with TTQP NPs. （i）Fluorescence imaging of guts after removing the abdominal skin. Bright-field（j） and NIR-Ⅱ fluorescence（k） images of the isolated stomachs and bowels from mice treated with PBS or LPS" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "54", "type": "bibr", "rid": "R54", "data": [ { "name": "text", "data": "54" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031785&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031795&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031790&type=", "width": "163.00000000", "height": "101.51916504", "fontsize": "" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "NIR-Ⅱ荧光分子设计常采用的策略之一是降低分子的带隙以实现波长的红移，但是不可避免地会导致QY下降。Li等通过“环稠化”策略来设计高亮度的NIR-Ⅱ AIE分子" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "54", "type": "bibr", "rid": "R54", "data": [ { "name": "text", "data": "54" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。如" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "（e）所示，TTQP由于扩展的共轭长度使得最大吸收和发射分别为683 nm和1 078 nm。如" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "（f）所示，相比于TTQ-DP，并环后的TTQP分子具有更刚性的平面和更延展的共轭长度，摩尔吸光系数增大的同时仍具有较好的AIE特性。如" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "（g）所示，TTQP NPs的亮度（QY与MEC的乘积）为26.52，远大于TTQ-DP NPs的15.81。随后，作者进一步评估了TTQP NPs在炎症肠道动物模型中的NIR-Ⅱ FLI能力。炎症肠道中，肠上皮细胞屏障功能的部分丧失反而使得其对纳米粒子的摄取能力增强。如" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "（h）所示，在饲喂荧光探针后3～48 h，肠炎部位显示出强烈的荧光信号。48 h后，去除腹部皮肤后仍然可以检测到荧光信号（" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "（i）），表明探针可用于肠炎的长期荧光监测。将小鼠处死后分离肠道进行离体FLI，肠道炎症的小鼠具有明显的荧光信号，而PBS处理的正常对照组小鼠无荧光信号（" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "（j）~(k））。因此，TTQP NPs有望通过NIR-Ⅱ FLI实现对动物模型中肠道炎症的无创检测。" } ] } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "3.3　其他疾病诊断" } ], "level": "2", "id": "s3c" } }, { "name": "p", "data": [ { "name": "text", "data": "除上述应用之外，NIR-Ⅱ AIE探针还可用于其他疾病的诊断，包括急性肺损伤" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "55", "type": "bibr", "rid": "R55", "data": [ { "name": "text", "data": "55" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、胰腺癌" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "56", "type": "bibr", "rid": "R56", "data": [ { "name": "text", "data": "56" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、出血性中风" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "57", "type": "bibr", "rid": "R57", "data": [ { "name": "text", "data": "57" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "和脑炎" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "58", "type": "bibr", "rid": "R58", "data": [ { "name": "text", "data": "58" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "等，展示了NIR-Ⅱ AIE探针强大的应用潜力。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "2021年，Zhang等开发了一种新型NIR-Ⅱ AIE分子THPP" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "55", "type": "bibr", "rid": "R55", "data": [ { "name": "text", "data": "55" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "（" }, { "name": "xref", "data": { "text": "图6", "type": "fig", "rid": "F6", "data": [ { "name": "text", "data": "图6" } ] } }, { "name": "text", "data": "（a）），THPP具有刚性平面以及J-聚集特性，可以同时提高MEC(2.4×10" }, { "name": "sup", "data": [ { "name": "text", "data": "5" } ] }, { "name": "text", "data": " L·mol" }, { "name": "sup", "data": [ { "name": "text", "data": "-1" } ] }, { "name": "text", "data": "·cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-1" } ] }, { "name": "text", "data": " )与QY (3.5%)，实现荧光亮度增强。此外，用不同的聚合物包覆（PEO" }, { "name": "sub", "data": [ { "name": "text", "data": "100" } ] }, { "name": "text", "data": "-PPO" }, { "name": "sub", "data": [ { "name": "text", "data": "65" } ] }, { "name": "text", "data": "-PEO" }, { "name": "sub", "data": [ { "name": "text", "data": "100" } ] }, { "name": "text", "data": "、" }, { "name": "sub", "data": [ { "name": "text", "data": " " } ] }, { "name": "text", "data": "F127、DSPE-PEG2000），可以得到不同的聚集状态（纳米乳剂、胶束）。J-聚集态的形成使得固态THPP的最大发射波长可以红移至1 152 nm（" }, { "name": "xref", "data": { "text": "图6", "type": "fig", "rid": "F6", "data": [ { "name": "text", "data": "图6" } ] } }, { "name": "text", "data": "（b））。如" }, { "name": "xref", "data": { "text": "图6", "type": "fig", "rid": "F6", "data": [ { "name": "text", "data": "图6" } ] } }, { "name": "text", "data": "（c）所示，寿命之间的细微变化归因于不同的聚集程度，胶束与固态具有相似的寿命时间，表明聚集程度相似，都形成了J-型聚集态。如" }, { "name": "xref", "data": { "text": "图6", "type": "fig", "rid": "F6", "data": [ { "name": "text", "data": "图6" } ] } }, { "name": "text", "data": "（d）~ （g）所示，在急性肺损伤模型中利用THPP胶束进行呼吸频率评估，根据荧光强度的变化，从肺振动信号中检测到肺损伤的小鼠呼吸频率比正常小鼠降低了76%，实现了对急性肺损伤的快速无创诊断。此外，THPP还可用于脑中风等疾病的诊断和预防。随后，作者将THPP胶束用于FeCl" }, { "name": "sub", "data": [ { "name": "text", "data": "3" } ] }, { "name": "text", "data": "诱导的左脑中风成像诊断（" }, { "name": "xref", "data": { "text": "图6", "type": "fig", "rid": "F6", "data": [ { "name": "text", "data": "图6" } ] } }, { "name": "text", "data": "（h））。结果表明，与商用近红外探针ICG相比，THPP胶束在左半球与右半球的荧光信号具有更明显差异（" }, { "name": "xref", "data": { "text": "图6", "type": "fig", "rid": "F6", "data": [ { "name": "text", "data": "图6" } ] } }, { "name": "text", "data": "（i）~（j）），体现了THPP胶束在临床诊断中的巨大潜力。" } ] }, { "name": "fig", "data": { "id": "F6", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图6" } ], "title": [ { "name": "text", "data": "（a）THPP的纳米乳液、胶束和固体的不同聚集程度（上）和THPP的AIE和J-聚集特征的象限图（下）；（b）F127胶束、纳米乳液和THPP固体的归一化发射光谱；（c）THPP的有机溶液、纳米乳剂、胶束和固体的寿命；（d）健康组肺组织切片；（f）急性肺损伤组肺组织切片；健康组（e）和急性肺损伤组（g）呼吸频率，插图：频率分析；（h）THPP胶束和ICG给药后小鼠左侧半球颈动脉血栓的 FLI；（i）THPP胶束组大脑半球的左（红）和右（蓝）脑半球NIR-Ⅱ的信号归一化图；（j）ICG组大脑半球的左（红）和右（蓝）脑半球的NIR-Ⅱ的信号归一化图" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "55", "type": "bibr", "rid": "R55", "data": [ { "name": "text", "data": "55" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.6" } ], "title": [ { "name": "text", "data": "（a）Scheme for the nanoemulsion, micelle and solid of THPP represent different aggregation extent, respectively（above） and quadrantal diagram for the special AIE and J-aggregation feature of THPP（below）.（b）Normalized emission spectra of F127 micelle, nanoemulsion, and solid of THPP.（c）Lifetime of organic solution, nanoemulsion, micelle, and solid of THPP.（d）Lung tissue sections stained of healthy group. （f）Lung tissue sections stained of acute-lung-injury group.Healthy group（e） and acute-lung-injury group（g） extracted from the region of lungs from the dorsal view. Inset is frequency analyzed from the variation after Fourier transform. A 0.5 Hz high-pass filter was used to calculate the respiratory rate.（h）Time-lapse FLI images of mice cerebral vasculature with carotid arterial thrombosis to the left hemisphere, after administration of THPP micelles and ICG.（i）Normalized NIR-Ⅱ signals in the left（red） and right（blue） cerebral hemispheres extracted from （e） using THPP micelles.（j）Normalized NIR-Ⅱ signals in the left（red） and right（blue） cerebral hemispheres extracted from （h） using ICG" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "55", "type": "bibr", "rid": "R55", "data": [ { "name": "text", "data": "55" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031799&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031806&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031802&type=", "width": "161.28833008", "height": "100.82867432", "fontsize": "" } ] } } ] } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "4　诊疗一体" } ], "level": "1", "id": "s4" } }, { "name": "p", "data": [ { "name": "text", "data": "诊疗一体化是指通过单一组分材料同时实现疾病诊断与治疗，极大地提升了疾病诊疗的效率与便捷性" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "59", "type": "bibr", "rid": "R59", "data": [ { "name": "text", "data": "59" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。与传统的诊疗分子相比，AIE探针不仅具有聚集荧光增强的特点，而且还可以实现激发态分子辐射跃迁与非辐射跃迁能量弛豫过程的动态调控，赋予探针分子PDT或者PTT的功能。通过结合NIR-Ⅱ穿透深度的优势，NIR-Ⅱ AIE探针可以实现对深层疾病的诊疗一体化，如FLI导航下的PDT或PTT，以及多模态成像指导的PDT与PTT的联合治疗。" } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "4.1　荧光成像指导的光动力诊疗" } ], "level": "2", "id": "s4a" } }, { "name": "p", "data": [ { "name": "text", "data": "PDT是指当光敏剂被光源激发后会由基态跃迁至激发态，而处于激发单线态（S" }, { "name": "sub", "data": [ { "name": "text", "data": "1" } ] }, { "name": "text", "data": "）的光敏剂可以通过系间串越（Intersystem crossing, ISC）途径跃迁至激发三线态（T" }, { "name": "sub", "data": [ { "name": "text", "data": "1" } ] }, { "name": "text", "data": "），随后与底物或周围氧分子之间进行第Ⅰ类（电子转移）或Ⅱ类（能量转移）转移产生高细胞毒性的ROS（" }, { "name": "sup", "data": [ { "name": "text", "data": "1" } ] }, { "name": "text", "data": "O" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "，H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "，·OH等），进而氧化损伤肿瘤细胞或者病原体，达到治疗疾病的目的" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "60", "type": "bibr", "rid": "R60", "data": [ { "name": "text", "data": "60" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "62", "type": "bibr", "rid": "R62", "data": [ { "name": "text", "data": "62" } ] } } ], "rid": [ "R60", "R61", "R62" ], "text": "60-62", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。传统的疏水性光敏剂（例如，卟啉和酞菁）在水性介质中容易聚集，分子间强π-π堆积作用会导致荧光猝灭以及降低ROS产生效率，造成诊断和治疗的效果不够理想" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "63", "type": "bibr", "rid": "R63", "data": [ { "name": "text", "data": "63" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。而AIE光敏剂在聚集状态下具备优异的FLI和ROS产生能力，是构建诊疗一体化平台的优异选择。由于NIR-Ⅱ FLI具有较深的穿透深度和较低的自发背景荧光，在诊疗方面表现出巨大的优势和应用前景" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "64", "type": "bibr", "rid": "R64", "data": [ { "name": "text", "data": "64" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "65", "type": "bibr", "rid": "R65", "data": [ { "name": "text", "data": "65" } ] } } ], "rid": [ "R64", "R65" ], "text": "64-65", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。然而，构建NIR-Ⅱ光敏剂常用的强电子受体会使得分子T" }, { "name": "sub", "data": [ { "name": "text", "data": "1" } ] }, { "name": "text", "data": "态能量低于激发" }, { "name": "sup", "data": [ { "name": "text", "data": "1" } ] }, { "name": "text", "data": "O" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "生成所需要的0.97 eV能量。因此，在NIR-Ⅱ区开发具有ROS的荧光探针仍然是一个挑战" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "66", "type": "bibr", "rid": "R66", "data": [ { "name": "text", "data": "66" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "68", "type": "bibr", "rid": "R68", "data": [ { "name": "text", "data": "68" } ] } } ], "rid": [ "R66", "R67", "R68" ], "text": "66-68", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。基于此，Lu等开发了具有A-D-A-D-A骨架分子BNET，其中丙二腈作为第一个电子受体，三苯胺作为电子给体，[3,4-乙撑二氧噻吩]（EDOT）作为π-桥，双硝基取代的苯并噻二唑作为第二个电子受体。探针在聚集态下由于扭转分子内电荷转移（Twisted intramolecular charge transfer, TICT）态的形成，波长可以红移至NIR-Ⅱ区，同时还可以保证足量的" }, { "name": "sup", "data": [ { "name": "text", "data": "1" } ] }, { "name": "text", "data": "O" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "生成" }, { "name": "sub", "data": [ { "name": "text", "data": " " } ] }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "69", "type": "bibr", "rid": "R69", "data": [ { "name": "text", "data": "69" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "（" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "（a））。如" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "（b）~(c）所示，将牛血清蛋白（Bovine serum albumin, BSA）与BNET以5∶1混合制备BNET NPs，与BSA/ICG复合体相比，BNET NPs可以产生更多的" }, { "name": "sup", "data": [ { "name": "text", "data": "1" } ] }, { "name": "text", "data": "O" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "，并且在激光持续照射30 min后荧光强度仍然可以保持在80%以上（" }, { "name": "xref", "data": { "text": "图 7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图 7" } ] } }, { "name": "text", "data": "（d））。随后，注射BNET NPs 24 h后，NIR-Ⅱ FLI可以很好地定位出原位结肠癌/胰腺癌小鼠的肿瘤位置，并且能够精准识别出发生转移的微小肿瘤（" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "（e）、（f））。如" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "（g）、（i）所示，在胰腺癌肿瘤模型中，NIR-Ⅱ FLI指导下的PDT可以高效地消除荷瘤小鼠的肿瘤。并且肿瘤离体切片的NIR-Ⅱ FLI表明，BNET NPs可以精准地富集在肿瘤区域（" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "（h））。因此，通过空间位阻效应促进TICT态的形成以延长发射波长，同时保持激发能产生足够的" }, { "name": "sup", "data": [ { "name": "text", "data": "1" } ] }, { "name": "text", "data": "O" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "，对开发NIR-Ⅱ区高活性氧探针具有重要指导意义。" } ] }, { "name": "fig", "data": { "id": "F7", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图7" } ], "title": [ { "name": "text", "data": "（a）BNET的分子设计机制示意图；（b）BNET NPs的透射电子显微镜图像；（c）BSA/ICG复合物和BNET NPs的活性氧产生能力；（d）BNET NPs与BSA/ICG复合物的光稳定性；（e）、（f）小鼠腹部皮肤切开暴露盲肠及邻近区域的盲肠原发肿瘤或转移瘤的NIR-Ⅱ FLI图；（g）利用BNET NPs对荷PANC-1-Luc胰腺癌裸鼠的术中近红外成像；（h）肿瘤切片的H" }, { "name": "text", "data": "&" }, { "name": "text", "data": "E染色和NIR-Ⅱ FLI，虚线圈：肿瘤区，T为肿瘤，N为正常胰腺组织；（i）Panc-1-Luc胰腺癌小鼠原位瘤经不同治疗后的生长曲线" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "69", "type": "bibr", "rid": "R69", "data": [ { "name": "text", "data": "69" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.7" } ], "title": [ { "name": "text", "data": "（a）Schematic diagram of the molecular mechanisms of the BNET. LE， locally excited state. TICT， twisted intramolecular charge transfer state. ISC， intersystem crossing between S" }, { "name": "sub", "data": [ { "name": "text", "data": "1" } ] }, { "name": "text", "data": " and T" }, { "name": "sub", "data": [ { "name": "text", "data": "1" } ] }, { "name": "text", "data": " states. Δ" }, { "name": "italic", "data": [ { "name": "text", "data": "E" } ] }, { "name": "sub", "data": [ { "name": "text", "data": "ST" } ] }, { "name": "text", "data": "， the energy difference between S" }, { "name": "sub", "data": [ { "name": "text", "data": "1" } ] }, { "name": "text", "data": " and T" }, { "name": "sub", "data": [ { "name": "text", "data": "1" } ] }, { "name": "text", "data": " states. Photodynamic therapeutic effect of BNET NPs " }, { "name": "italic", "data": [ { "name": "text", "data": "in vitro" } ] }, { "name": "text", "data": ". （b）TEM of BNET NPs. （c）Relative fluorescence intensity of SOSG in BSA/ICG complex or BNET NPs with or without the laser irradiation for 10 min. Data are mean ±SD（" }, { "name": "italic", "data": [ { "name": "text", "data": "n" } ] }, { "name": "text", "data": "=3）. （d）Comparison of the photostability between BNET NPs and BSA/ICG complex. Plot of " }, { "name": "italic", "data": [ { "name": "text", "data": "I" } ] }, { "name": "text", "data": "/" }, { "name": "italic", "data": [ { "name": "text", "data": "I" } ] }, { "name": "sub", "data": [ { "name": "text", "data": "0" } ] }, { "name": "text", "data": " " }, { "name": "italic", "data": [ { "name": "text", "data": "versus" } ] }, { "name": "text", "data": " irradiation time. （e），（f）Intravital NIR-Ⅱ imaging of cecal primary tumors or metastases in mouse abdominal skin incision to expose the cecum and adjacent regions. （g）NIR-Ⅱ image-guided PDT of nude mice bearing orthotopic Panc-1-Luc human pancreatic tumor by BNET NPs. （h）H" }, { "name": "text", "data": "&" }, { "name": "text", "data": "E staining and NIR-Ⅱ live imaging of the tumor section. （i）Tumor growth curves of mice bearing orthotopic Panc-1-Luc pancreatic cancer following different treatment measured by the bioluminescence" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "69", "type": "bibr", "rid": "R69", "data": [ { "name": "text", "data": "69" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031811&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031818&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031814&type=", "width": "163.27288818", "height": "80.23999023", "fontsize": "" } ] } } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "4.2　荧光成像引导光热诊疗" } ], "level": "2", "id": "s4b" } }, { "name": "p", "data": [ { "name": "text", "data": "PTT是一种有效治疗癌症的方式，光热试剂在激光等电磁辐射下，将吸收的光子能量转化为热量，通过局部过热效应实现肿瘤的精准消融" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "70", "type": "bibr", "rid": "R70", "data": [ { "name": "text", "data": "70" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。研究表明，NIR-Ⅱ FLI引导的PTT具有成像分辨率高、侵入性小、精准可控等优点，可以极大地提高诊断的准确性和疾病的治疗效率" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "71", "type": "bibr", "rid": "R71", "data": [ { "name": "text", "data": "71" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "72", "type": "bibr", "rid": "R72", "data": [ { "name": "text", "data": "72" } ] } } ], "rid": [ "R71", "R72" ], "text": "71-72", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。组成AIE分子的多转子基元通过自由转动，可以将光能部分转化为热能" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "73", "type": "bibr", "rid": "R73", "data": [ { "name": "text", "data": "73" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "74", "type": "bibr", "rid": "R74", "data": [ { "name": "text", "data": "74" } ] } } ], "rid": [ "R73", "R74" ], "text": "73-74", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。此外，随着发射波长的红移，激发态能量更倾向于通过非辐射耗散通道衰退" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "75", "type": "bibr", "rid": "R75", "data": [ { "name": "text", "data": "75" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "76", "type": "bibr", "rid": "R76", "data": [ { "name": "text", "data": "76" } ] } } ], "rid": [ "R75", "R76" ], "text": "75-76", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。因此，相比可见光与近红外一区，NIR-Ⅱ AIE探针更适合用于PTT。药物靶向递送可以最大程度地减少对正常组织的伤害，降低潜在的毒副作用。而目前荧光探针的递送过于依靠EPR效应，对疾病部位的特异性靶向能力不足。为此，Lin等开发了一种由TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs与肿瘤细胞衍生的“外泌体帽”（Exosomes, EXO）组成的混合纳米囊泡（TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXOs），使探针具有特异性靶向能力" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "77", "type": "bibr", "rid": "R77", "data": [ { "name": "text", "data": "77" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。首先，作者研究了TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXOs在CT26荷瘤小鼠模型中的NIR-Ⅱ FLI效果。将TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs和TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXOs分别注射到小鼠体内后，如" }, { "name": "xref", "data": { "text": "图8", "type": "fig", "rid": "F8", "data": [ { "name": "text", "data": "图8" } ] } }, { "name": "text", "data": "（b）所示，TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXO组的肿瘤可以观察到明显的荧光信号，而TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs组小鼠肿瘤只能看到微弱的荧光信号，表明EXO赋予TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs优异的肿瘤靶向能力。随后又评估了TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXOs用于NIR-Ⅱ FLI指导的PTT效果。如" }, { "name": "xref", "data": { "text": "图8", "type": "fig", "rid": "F8", "data": [ { "name": "text", "data": "图8" } ] } }, { "name": "text", "data": "（c）~（d）所示，将TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXOs注射到小鼠体内后，由于纳米探针优异的肿瘤靶向效果，NIR-Ⅱ FLI可以精准地引导激光对肿瘤进行照射，减少对邻近正常组织的损伤。小鼠肿瘤区域的温度在激光照射10 min内迅速升至57 ℃。如" }, { "name": "xref", "data": { "text": "图8", "type": "fig", "rid": "F8", "data": [ { "name": "text", "data": "图8" } ] } }, { "name": "text", "data": "（e）所示，与所有其他对照组相比，TT3-" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXOs + 激光治疗组的小鼠肿瘤明显得以抑制甚至根除，显示出优良的同源靶向能力和PTT性能。血脑屏障（Blood brain barrier, BBB）是一种大脑血管、细胞等组成大脑组织之间的保护性屏障，但是保护也是有代价的，当面临诸如脑胶质瘤（Glioblastoma multiforme, GBM）等威胁时，BBB会干扰免疫系统，同时阻碍药物进入，因此BBB的存在是GBM治疗中一个难以突破的挑战" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "79", "type": "bibr", "rid": "R79", "data": [ { "name": "text", "data": "79" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "81", "type": "bibr", "rid": "R81", "data": [ { "name": "text", "data": "81" } ] } } ], "rid": [ "R79", "R80", "R81" ], "text": "79-81", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。2022年，Tang等将脑靶向的多肽载脂蛋白E肽（Apolipoprotein E, ApoE）嫁接到Ph上组成ApoE-Ph NPs，能够有效地促进纳米探针穿越BBB，实现对GBM的靶向给药（8（f））" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "78", "type": "bibr", "rid": "R78", "data": [ { "name": "text", "data": "78" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。此外，通过分子结构的调控可以使分子同时满足FLI与PTT的需求。如" }, { "name": "xref", "data": { "text": "图8", "type": "fig", "rid": "F8", "data": [ { "name": "text", "data": "图8" } ] } }, { "name": "text", "data": "（g）所示，与Ph NPs相比，ApoE-Ph NPs在原位脑胶质瘤荷瘤小鼠模型中显示出更加明亮的NIR-Ⅱ荧光，并且可以持续48 h以上，展示出长效的示踪能力。在较低功率（0.5 W ·cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-2" } ] }, { "name": "text", "data": "）激光照射5 min后，肿瘤处温度升高至41 ℃，表现出优异的光热性能（" }, { "name": "xref", "data": { "text": "图8", "type": "fig", "rid": "F8", "data": [ { "name": "text", "data": "图8" } ] } }, { "name": "text", "data": "（f））。在NIR-Ⅱb FLI导航下进行PTT后，GBM的生长被明显抑制（" }, { "name": "xref", "data": { "text": "图8", "type": "fig", "rid": "F8", "data": [ { "name": "text", "data": "图8" } ] } }, { "name": "text", "data": "（i））。ApoE-Ph NPs的设计开发为原位GBM的精准诊疗提供了可能，并有望用于更多脑部疾病的诊疗。" } ] }, { "name": "fig", "data": { "id": "F8", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图8" } ], "title": [ { "name": "text", "data": "（a）肿瘤细胞衍生的EXO与TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP杂化的纳米粒子示意图；（b）TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs和TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXOs的小鼠体内NIR⁃Ⅱ FLI图；（c）CT26荷瘤小鼠体内皮下肿瘤部位在808 nm激光照射下不同材料的时间⁃温度曲线；（d）静脉注射PBS、EXO、TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB纳米粒子和TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXOs的小鼠PTI" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "77", "type": "bibr", "rid": "R77", "data": [ { "name": "text", "data": "77" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "；（e）不同处理后小鼠相对肿瘤体积Group 1：PBS，Group 2：PBS + Laser，Group 3：EXO，Group 4：EXO + Laser，Group 5：TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs，Group 6：TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs + Laser，Group 7：TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs@EXOs，Group 8：TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs@EXOs + Laser；（f）脑靶向脂质蛋白ApoE⁃Ph纳米粒子制备与PTT机制示意图；（g）注射Ph纳米粒子或ApoE⁃Ph纳米粒子后肿瘤的NIR⁃Ⅱ FLI图；（h）PBS、Ph纳米粒子或ApoE⁃Ph纳米粒子在预定时间点照射后活体PTI；（i）肿瘤处发光值的量化图" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "78", "type": "bibr", "rid": "R78", "data": [ { "name": "text", "data": "78" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.8" } ], "title": [ { "name": "text", "data": "（a）Schematic illustration of tumor cell⁃derived EXO/TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP hybrid nanovesicles.（b）" }, { "name": "italic", "data": [ { "name": "text", "data": "In vivo" } ] }, { "name": "text", "data": " biodistribution of TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs and TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXOs. Representative NIR⁃Ⅱ fluorescence images of CT26 tumor⁃bearing mice 24 h after the" }, { "name": "italic", "data": [ { "name": "text", "data": " i.v." } ] }, { "name": "text", "data": " administration of TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs（left）and TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXOs（right）.（c）" }, { "name": "italic", "data": [ { "name": "text", "data": "In vivo" } ] }, { "name": "text", "data": " PTT on CT26 tumor⁃bearing mice. Temperature curves of the subcutaneous tumor sites of the mice intravenously injected with EXO, PBS, TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs and TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXOs with continuous laser irradiation（808 nm, 1.0 W·cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-2" } ] }, { "name": "text", "data": ", 10 min）.（d）Infrared thermal images of mice intravenously injected with PBS, EXO, TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs and TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NP@EXOs, followed by laser irradiation（808 nm, 1.0 W· cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-2" } ] }, { "name": "text", "data": "） 24 h post injection for 0, 2, 4, 6， 10 min.（e）Relative tumor volumes of the mice after different treatments. Group 1: PBS，Group 2: PBS+Laser，Group 3: EXO，Group 4: EXO+Laser，Group 5: TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs，Group 6: TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs+Laser，Group 7: TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs@EXOs，Group 8: TT3⁃" }, { "name": "italic", "data": [ { "name": "text", "data": "o" } ] }, { "name": "text", "data": "CB NPs@EXOs+Laser.（f）Fabrication of brain⁃targeting ApoE⁃Ph NPs, NIR⁃Ⅱb imaging at 1 550 nm, and photothermal therapy of mice bearing orthotopic glioblastoma.（g）" }, { "name": "italic", "data": [ { "name": "text", "data": "In vivo" } ] }, { "name": "text", "data": " bioluminescence of tumor showing real⁃time accumulation of various nanoparticles in GBM tumor（black dashed line） at different times post⁃injection （dosage:10 mg·kg" }, { "name": "sup", "data": [ { "name": "text", "data": "-1" } ] }, { "name": "text", "data": "）.（h）" }, { "name": "italic", "data": [ { "name": "text", "data": "In vivo" } ] }, { "name": "text", "data": " photothermal imaging upon irradiation（808 nm, 0.5 W·cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-2" } ] }, { "name": "text", "data": "） after treatment with PBS, Ph NPs, or ApoE⁃Ph NPs at predetermined time points.（i）Quantification of luminescence values at the tumor" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "78", "type": "bibr", "rid": "R78", "data": [ { "name": "text", "data": "78" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031821&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031826&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031823&type=", "width": "161.04895020", "height": "72.86755371", "fontsize": "" } ] } } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "4.3　多模态诊疗" } ], "level": "2", "id": "s4c" } }, { "name": "p", "data": [ { "name": "text", "data": "多模态诊疗是集多模态成像（FLI、PAI和PTI）与多模态治疗（PDT和PTT）于一体的诊疗方式" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "82", "type": "bibr", "rid": "R82", "data": [ { "name": "text", "data": "82" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。与单一模态的成像或者治疗相比，多模态诊疗可以更好地提高诊断的准确性和治疗的效率，因而成为诊疗领域的一大发展趋势。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "目前构建多模态光学诊疗系统最常用的策略是将具有单一功能的多种组分组合到一个纳米平台，然而这种方法不可避免地会受到成分复杂、重复性差的限制，难以进行临床转化" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "83", "type": "bibr", "rid": "R83", "data": [ { "name": "text", "data": "83" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。因此，设计集多种功能于一体的智能分子，构建单组分的多功能光学诊疗系统具有重大意义" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "82", "type": "bibr", "rid": "R82", "data": [ { "name": "text", "data": "82" } ] } }, { "name": "text", "data": "," }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "84", "type": "bibr", "rid": "R84", "data": [ { "name": "text", "data": "84" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "85", "type": "bibr", "rid": "R85", "data": [ { "name": "text", "data": "85" } ] } } ], "rid": [ "R84", "R85" ], "text": "84-85", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。根据Jablonski图，AIE分子被激发后能量的耗散可以通过辐射跃迁通道提供FLI，或非辐射跃迁通道提供光PAI、PTI和PTT，亦或通过ISC过程产生ROS用于PDT" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "86", "type": "bibr", "rid": "R86", "data": [ { "name": "text", "data": "86" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "87", "type": "bibr", "rid": "R87", "data": [ { "name": "text", "data": "87" } ] } } ], "rid": [ "R86", "R87" ], "text": "86-87", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。AIE分子特有的多转子结构有助于实现辐射与非辐射能量耗散过程的可控平衡，从而“按需”构建多转子结构模态诊疗平台。" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "（a）所示为近些年报道的NIR-Ⅱ AIE诊疗一体化探针，如BITT" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "88", "type": "bibr", "rid": "R88", "data": [ { "name": "text", "data": "88" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、TSSI" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "89", "type": "bibr", "rid": "R89", "data": [ { "name": "text", "data": "89" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、TSSAM" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "90", "type": "bibr", "rid": "R90", "data": [ { "name": "text", "data": "90" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、TTT-4" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "91", "type": "bibr", "rid": "R91", "data": [ { "name": "text", "data": "91" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、ZSY-TPE" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "92", "type": "bibr", "rid": "R92", "data": [ { "name": "text", "data": "92" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、DPBTA-DPTQ" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "93", "type": "bibr", "rid": "R93", "data": [ { "name": "text", "data": "93" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "、TPA-BT-DPTQ" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "94", "type": "bibr", "rid": "R94", "data": [ { "name": "text", "data": "94" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "等" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "95", "type": "bibr", "rid": "R95", "data": [ { "name": "text", "data": "95" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "96", "type": "bibr", "rid": "R96", "data": [ { "name": "text", "data": "96" } ] } } ], "rid": [ "R95", "R96" ], "text": "95-96", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "，极大地丰富扩展了多模态NIR-Ⅱ AIE探针库。其中Tang等首次开创了基于单个AIE分子的“全能”探针TSSI" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "89", "type": "bibr", "rid": "R89", "data": [ { "name": "text", "data": "89" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。在激光照射下，TSSI NPs表现出明亮的NIR-Ⅱ荧光信号、优异的ROS产生能力和光热转化效率。体外和体内研究均证实，NIR-Ⅱ AIE NPs在生物医学应用中发挥着出色的诊疗效果。" } ] }, { "name": "fig", "data": { "id": "F9", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图9" } ], "title": [ { "name": "text", "data": "（a）具有诊疗一体化功能代表性的NIR-Ⅱ AIE分子结构式；（b）TPEDCAc分子结构、纳米制备和多功能光疗应用示意图；（c）TPEDCAc的体外活性氧产生能力；（d）TPEDCAc在水溶液中光热循环的稳定性；（e）、（f）TPEDCAc与MCF-7细胞孵育后的细胞活力与共聚焦成像效果；（g）660 nm激光照射下，TPEDCAc瘤内给药后不同时间点小鼠的NIR-Ⅱ FLI；（h）肿瘤内注射TPEDCAc后MCF-7荷瘤小鼠的光声成像；（i）MCF-7荷瘤小鼠瘤内注射TPEDCAc 12 h后，660 nm激光照射下不同时间点的PTI图" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "97", "type": "bibr", "rid": "R97", "data": [ { "name": "text", "data": "97" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.9" } ], "title": [ { "name": "text", "data": "（a）Representative NIR-Ⅱ AIE molecules with therapeutic integration function. （b）Schematic diagram of the molecular structure， nanofabrication and multifunctional phototherapy application of multimodal therapeutic AIE. （c）ROS generation of AIE aggregates（10×10" }, { "name": "sup", "data": [ { "name": "text", "data": "-6" } ] }, { "name": "text", "data": " m） upon laser irradiation（660 nm， 0.3 W·cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-2" } ] }, { "name": "text", "data": "） using DCFH-DA（40×10" }, { "name": "sup", "data": [ { "name": "text", "data": "-6" } ] }, { "name": "text", "data": " m） as an indicator. （d）Temperature elevation of TPEDCAc aggregates（200×10" }, { "name": "sup", "data": [ { "name": "text", "data": "-6 " } ] }, { "name": "text", "data": "m） in aqueous solution under five irradiation-cooling cycles（660 nm， 0.3 W·cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-2" } ] }, { "name": "text", "data": "）. （e）， （f）Cell viability and CLSM images of MCF-7 cells incubated with TPEDCAc aggregates. （g）NIR-Ⅱ FLI of the mice at different time after intratumoral administration of TPEDCAc aggregates under laser irradiation（660 nm， 0.3 W·cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-2" } ] }, { "name": "text", "data": "）. （h）PA imaging of MCF-7 tumor-bearing mice after intratumoral injection of TPEDCAc aggregates（1×10" }, { "name": "sup", "data": [ { "name": "text", "data": "-3" } ] }, { "name": "text", "data": " m， 20 µL）. （i）Infrared thermal images of MCF-7 tumor-bearing mice intratumorally injected with TPEDCAc aggregates followed by（12 h later） laser irradiation（660 nm， 0.3 W·cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-2" } ] }, { "name": "text", "data": "） for 1， 3， 4， 5 min" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "97", "type": "bibr", "rid": "R97", "data": [ { "name": "text", "data": "97" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031829&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031835&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=41031832&type=", "width": "156.00500488", "height": "121.35253906", "fontsize": "" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "2022年，Tang等基于电子受体工程策略，开发出具有高灵敏度的NIR-Ⅱ AIE聚集体（TPEDCAc）" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "97", "type": "bibr", "rid": "R97", "data": [ { "name": "text", "data": "97" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "，实现了FLI、PAI、PTI多模态成像指导的PDT和PTT协同治疗。如" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "（b）所示，首先在分子中引入了一对高度扭曲的三苯乙烯和二苯胺单元，防止分子间π-π堆积，确保AIE特性；并且通过控制三苯乙烯和二苯胺单元的分子内运动，平衡辐射与非辐射耗散激发态能量，以实现光诊疗效果的最佳化。此外，通过增加受体吸电子能力，从吡啶鎓、喹啉鎓到吖啶鎓，分子内电荷转移（ICT）效应显著增强，从而达到NIR-Ⅱ的强发射。通过2′,7′二氯荧光素二乙酸酯（DCFH-DA）来测试探针的活性氧产生能力。如" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "（c）所示，TPEDCAc的ROS产生效率与对照组相比最强且速度最快。如" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "（d），TPEDCAc NPs在激光照射5 min后温度升高至47 ℃，表现出优异的光热性能和光热稳定性。随后在细胞层面进行了生物安全性验证，如" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "（e）所示，在660 nm激光照射10 min后，TPEDCAc在15 µg·mL" }, { "name": "sup", "data": [ { "name": "text", "data": "-1" } ] }, { "name": "text", "data": "的浓度下可以杀死" }, { "name": "text", "data": ">" }, { "name": "text", "data": "90% 的MCF-7细胞;而在黑暗条件下，即使在高浓度下细胞存活率也保持在90%，表明TPEDCAc具有良好的可控光疗效果和良好的生物相容性。研究表明，肿瘤的线粒体与细胞应激、信号传导等密切相关，因此针对肿瘤细胞线粒体的靶向治疗对现代癌症治疗具有重要意义。由于线粒体膜电位的负电性，阳离子型探针可以很好地富集在线粒体中。如" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "（f）所示，通过线粒体绿色荧光探针共定位实验证明了TPEDCAc纳米探针可以特异性地靶向线粒体。瘤内注射TPEDCAc纳米探针后，在660 nm激光照射下肿瘤区域显示出明亮的NIR-Ⅱ荧光信号，即使在48 h后也可以清楚地看到肿瘤，体现了荧光探针在肿瘤中优异的长期示踪能力（" }, { "name": "xref", "data": { "text": "图 9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图 9" } ] } }, { "name": "text", "data": "（g））。此外，PAI也可以很好地定位出肿瘤的位置（" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "（h））。随后，作者又评估了荧光探针的光热性能，持续光照5 min后，小鼠肿瘤表面温度可以上升至53.8 ℃，可用于PTT（" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "（i））。随后，通过多模态指导下的PDT和PTT联合治疗，成功抑制了小鼠肿瘤的生长，为新型多模态诊疗探针的设计提供了有效策略。" } ] } ] } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "5　总结与展望" } ], "level": "1", "id": "s5" } }, { "name": "p", "data": [ { "name": "text", "data": "得益于NIR-Ⅱ荧光探针更深的组织穿透性，NIR-Ⅱ分子在光学诊疗中表现出巨大的潜力。传统的荧光探针由于在生物体内环境中会发生聚集，导致荧光猝灭以及ROS效率低下。而具有AIE特性的探针可以完美地解决这一问题，其独特的扭曲结构使得分子在聚集态可以有效避免分子间π-π堆积，表现出ROS与荧光增强的效果。具有AIE特性的NIR-Ⅱ荧光探针兼具两者的优势，在荧光活体成像、疾病诊断和疾病诊疗一体化等生物医学领域展现出巨大的应用潜力。虽然NIR-Ⅱ AIE荧光探针在疾病的诊疗中已成为一颗冉冉升起的“新星”，但是其发展仍处于早期阶段，存在许多不足与挑战。首先，AIE探针能够提升分子在聚集态下的QY，但是AIE分子固有的扭曲结构使得MEC较小，导致探针的整体亮度无法大幅度提升。因此如何设计具有高QY和高MEC的AIE材料或者更好地调控它们两者之间的关系有待进一步研究。此外，新型分子骨架和设计策略亟待扩展。目前NIR-Ⅱ AIE探针大都是基于电子给体和电子受体工程策略构建的具有D-A或者D-A-D骨架的分子，新型分子骨架的开发或聚集态行为的调控（如J-聚集态或TICT态）将会丰富NIR-Ⅱ AIE探针的种类。其次，目前报道的NIR-Ⅱ AIE探针的激发波长大都局限于可见光与NIR-Ⅰ区域，能被NIR-Ⅱ光激发的AIE探针毫无疑问将为更深层组织疾病的诊疗提供可能。另外，含有活性官能团如—COOH、—N" }, { "name": "sub", "data": [ { "name": "text", "data": "3" } ] }, { "name": "text", "data": "、—NH" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "等NIR-Ⅱ AIE分子的高效合成为进一步的功能化修饰提供了可能，将会极大地丰富其在生物医学中应用。再者，NIR-Ⅱ AIE纳米探针系统性的药代动力学和毒理学评估将会进一步推动其临床转化；而目前开发的NIR-Ⅱ AIE探针大多通过EPR的被动靶向效应到达病灶部位，限制了临床上的应用。因此开发更多的主动靶向策略，提高探针对特异性疾病的靶向能力，将会大大提升疾病诊断的准确性和效率，降低潜在的毒副作用。最后，目前利用NIR-Ⅱ AIE探针进行疾病诊断与治疗的模型仍非常有限，未来使用NIR-Ⅱ AIE探针尝试更多疾病模型的诊疗将会成为本领域的研究热点之一。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "综上所述，我们相信，在科研人员共同努力下，NIR-Ⅱ AIE纳米探针在不久的将来会发挥更加重要的作用。希望这篇综述能使读者全面了解NIR-Ⅱ AIE探针在生物医学应用中的最新进展，激发更多的研究热情，共同开发出性能更加优异的NIR-Ⅱ AIE材料，满足不同生物医学应用场景的性能需求，让NIR-Ⅱ AIE这颗“闪耀的新星”继续“点亮”纳米医学的天空。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "本文专家审稿意见及作者回复内容的下载地址：" }, { "name": "extlink", "data": { "text": [ { "name": "text", "data": 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