Application of NIR-II Aggregation Induced Emission Materials in Surgical Navigation

LIU Xiao-chun; LI Hai-rong; TANG Hui; LYU Ya-jing; ZHANG Ya-hui; WANG Zhou-yu

doi:10.37188/CJL.20220432

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Application of NIR-II Aggregation Induced Emission Materials in Surgical Navigation

Updated：2023-02-03

- Application of NIR-II Aggregation Induced Emission Materials in Surgical Navigation Enhanced Publication
- Chinese Journal of Luminescence Vol.null, Issue null, (2023)
- Affiliations：
  
  Department of Chemistry， Xihua University,Chengdu,China,610039
- Author bio：
- Funds：
  
  National Natural Science Foundation of China(21905021);Sichuan Province Science and Technology Support Program(2022NSFSC1269;2023NSFSC1977)
- DOI：10.37188/CJL.20220432 CLC： O482.31
- Published Online：03 February 2023，
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刘小春,李海蓉,唐会等.近红外二区聚集诱导发光材料在手术导航上的应用[J].发光学报,

LIU Xiao-chun,LI Hai-rong,TANG Hui,et al.Application of NIR-II Aggregation Induced Emission Materials in Surgical Navigation[J].Chinese Journal of Luminescence,
刘小春,李海蓉,唐会等.近红外二区聚集诱导发光材料在手术导航上的应用[J].发光学报, DOI：10.37188/CJL.20220432

LIU Xiao-chun,LI Hai-rong,TANG Hui,et al.Application of NIR-II Aggregation Induced Emission Materials in Surgical Navigation[J].Chinese Journal of Luminescence, DOI：10.37188/CJL.20220432

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At present， visual observation and ultrasonic technology are commonly used by surgeons to determine tumor boundaries， residual lesions and micrometastasis lesions， which cause cancer recurrence to a large extent. The rapid development of the second near-infrared （NIR-II） aggregation-induced emission （AIE） materials as fluorescent surgery navigation reagents provides new avenue to solve the problem. In this review， structural design of NIR-II AIE materials in surgical navigation are first summarized. Then the application of NIR-II AIE material in tumor resection surgery， in detection of lymph node resection surgery， and in other tissues are discussed. At last， the future development of NIR-II AIE materials in surgical navigation are prospected." } ] } ] } ], "keyword": [ { "lang": "zh", "data": [ [ { "name": "text", "data": "近红外二区" } ], [ { "name": "text", "data": "聚集诱导发光" } ], [ { "name": "text", "data": "手术导航" } ], [ { "name": "text", "data": "供体" } ], [ { "name": "text", "data": "受体" } ] ] }, { "lang": "en", "data": [ [ { "name": "text", "data": "the second near-infrared" } ], [ { "name": "text", "data": "aggregation-induced emission" } ], [ { "name": "text", "data": "surgical navigation" } ], [ { "name": "text", "data": "donor" } ], [ { "name": "text", "data": "acceptor" } ] ] } ], "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": "手术仍然是目前绝大多数实体瘤的主要治疗方法。据研究表明80%以上的癌症患者至少接受过一次手术治疗" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "1", "type": "bibr", "rid": "R1", "data": [ { "name": "text", "data": "1" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。目前肿瘤手术切除主要面临的两个问题：1）在手术切除中，外科医生难以通过触诊和目视检查等手段来精准区分肿瘤边缘，尤其是微小肿瘤(如直径小于1 mm)，导致正常组织过度切除或肿瘤组织不完全切除；2）在手术切除后，临床上缺乏有效的检测手段反馈病人术后的肿瘤复发、转移等情况" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "2", "type": "bibr", "rid": "R2", "data": [ { "name": "text", "data": "2" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。所以，如何提高手术过程中的切除率以及术后的有效评估，是目前肿瘤手术亟须解决的问题。手术导航试剂可以起到术前诊断，术中辅助切除病灶以及术后效果评估“三位一体”的作用。传统的手术导航以计算机断层扫描(CT)、正电子发射断层扫描(PET)和磁共振成像(MRI)等医学影像数据为基础，提高了手术的效率和精准" }, { "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": "。但是，上述成像方式很难整合至手术场景中" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "4", "type": "bibr", "rid": "R4", "data": [ { "name": "text", "data": "4" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "，并且具有一定的局限性，如CT和PET具有电离辐射、MRI和PET的成本昂贵" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "5", "type": "bibr", "rid": "R5", "data": [ { "name": "text", "data": "5" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "等。因此开发新型的安全的手术导航试剂逐渐成为研究的热点。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "由于具有较高的时空分辨力，光学成像探针成为手术导航试剂的最佳选择之一" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "6", "type": "bibr", "rid": "R6", "data": [ { "name": "text", "data": "6" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "7", "type": "bibr", "rid": "R7", "data": [ { "name": "text", "data": "7" } ] } } ], "rid": [ "R6", "R7" ], "text": "6-7", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。然而，穿透深度弱以及聚集诱导荧光猝灭(ACQ)现象限制了传统荧光材料作为手术导航试剂的发展" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "8", "type": "bibr", "rid": "R8", "data": [ { "name": "text", "data": "8" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。直到2001年唐本忠教授发现了聚集诱导发光(AIE)现象" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "9", "type": "bibr", "rid": "R9", "data": [ { "name": "text", "data": "9" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "使得荧光材料在生物诊疗应用中有了突飞猛进的发展" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "10", "type": "bibr", "rid": "R10", "data": [ { "name": "text", "data": "10" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "15", "type": "bibr", "rid": "R15", "data": [ { "name": "text", "data": "15" } ] } } ], "rid": [ "R10", "R11", "R12", "R13", "R14", "R15" ], "text": "10-15", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。并且，在众多科学家的努力下，AIE材料的发光波长扩展到了近红外二区(NIR-II,1000-1700 nm)" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "16", "type": "bibr", "rid": "R16", "data": [ { "name": "text", "data": "16" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "18", "type": "bibr", "rid": "R18", "data": [ { "name": "text", "data": "18" } ] } } ], "rid": [ "R16", "R17", "R18" ], "text": "16-18", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。NIR-II AIE的荧光材料具有组织穿透能力强(约5-20 mm)、背景光干扰小、对生物组织无光损伤等优点，很好的解决了传统荧光手术导航试剂的穿透深度浅、受生物自发光的干扰和ACQ的问题" }, { "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": "，在手术导航中实现了“1+1" }, { "name": "text", "data": ">" }, { "name": "text", "data": "2”的效果。除此之外，与含有重金属的NIR-II荧光探针相比，NIR-II AIE材料的毒性更低，生物相容性更好" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "20", "type": "bibr", "rid": "R20", "data": [ { "name": "text", "data": "20" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "21", "type": "bibr", "rid": "R21", "data": [ { "name": "text", "data": "21" } ] } } ], "rid": [ "R20", "R21" ], "text": "20-21", "type": "bibr" } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。综上所述，NIR-II AIE手术导航试剂有望进一步应用在临床的手术中，实现术前诊断、术中辅助和术后评估三位一体。本文结合最新的研究进展，主要总结了NIR-II AIE发光分子设计以及NIR-II AIE材料在手术导航中的应用。" } ] } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2　NIR-II AIE材料应用于手术导航" } ], "level": "1", "id": "s2" } }, { "name": "p", "data": [ { "name": "text", "data": "AIE材料发射波长要达到NIR-II，分子设计至关重要。目前大多数NIR-II AIE荧光分子采取供体-受体-供体(D-A-D)结构。D-A-D结构具有很强的分子内电荷转移作用(ICT), 能够显著降低分子能隙，使得分子吸收和发射红移。同时扭曲的分子结构不仅抑制了分子间π-π堆积保证其AIE特性，还能红移发射波长使其达到NIR-II。苯并双噻二唑(BBTD)类化合物由于具有强的缺电子性能通常被用作强受体。基于BBTD作为电子受体，通过改变供体结构和共轭分子长度来红移发射波长到NIR-II区域。因此NIR-II AIE荧光材料在用于手术导航时可以穿透较深的组织深度，更准确清楚的区分正常组织与病灶部位，并且在术中切除时减少对正常组织的伤害，进一步提高手术切除率。本综述主要分析不同NIR-II AIE分子结构特点以及其在不同部位手术导航的应用 (" }, { "name": "xref", "data": { "text": "图1", "type": "fig", "rid": "F1", "data": [ { "name": "text", "data": "图1" } ] } }, { "name": "text", "data": ")。" } ] }, { "name": "fig", "data": { "id": "F1", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图1" } ], "title": [ { "name": "text", "data": "NIR-II AIE材料的手术导航应用" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.1" } ], "title": [ { "name": "text", "data": "Surgical navigation application of NIR-II AIE materials" } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481294&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481296&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481295&type=", "width": "77.69583130", "height": "76.30141449", "fontsize": "" } ] } }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2.1　NIR-II AIE材料在肿瘤切除手术中的应用" } ], "level": "2", "id": "s2a" } }, { "name": "p", "data": [ { "name": "text", "data": "为了在手术中将癌症完全切除，外科医生必须快速准确地识别肿瘤边界，但医生很难用肉眼检测到一些癌症在早期阶段的微转移。基于BBTD的NIR-II AIE成像可作为术前诊断和术中导航的理想选择，帮助外科医生识别和切除肿瘤，作为外科医生的第三只眼" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "22", "type": "bibr", "rid": "R22", "data": [ { "name": "text", "data": "22" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。Jia课题组以BBTD为受体合成了NIR-II分子PTZ-TQ (" }, { "name": "xref", "data": { "text": "图2", "type": "fig", "rid": "F2", "data": [ { "name": "text", "data": "图2" } ] } }, { "name": "text", "data": "a) " }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "23", "type": "bibr", "rid": "R23", "data": [ { "name": "text", "data": "23" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "，D-A-D结构使PTZ-TQ分子表现出优异的吸收性能,在四氢呋喃(THF)中最大吸收波长达到650 nm (" }, { "name": "xref", "data": { "text": "图2", "type": "fig", "rid": "F2", "data": [ { "name": "text", "data": "图2" } ] } }, { "name": "text", "data": "b)。随着水含量的增加其荧光强度逐渐增强，具有典型的AIE特性。并且其发射波长达1050 nm (" }, { "name": "xref", "data": { "text": "图2", "type": "fig", "rid": "F2", "data": [ { "name": "text", "data": "图2" } ] } }, { "name": "text", "data": "c)。以DSPE-PEG" }, { "name": "sub", "data": [ { "name": "text", "data": "3400" } ] }, { "name": "text", "data": "-NH" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "为基质封装的PTZ-TQ-AIE纳米粒子(PTZ-TQ-AIE NPs)(荧光量子产率Φ" }, { "name": "sub", "data": [ { "name": "text", "data": "f" } ] }, { "name": "text", "data": "=0.3%)也表现出高稳定性和良好的抗光漂白性。将PTZ-TQ-AIE NPs通过静脉注射到小鼠体内，在手术前通过NIR-II荧光成像对小鼠进行诊断，可以清晰分辨出肿瘤与正常组织的边界。在手术过程中以PTZ-TQ-AIE NPs的近红外二区荧光成像作为手术导航，能够更准确的进行肿瘤手术切除，进一步加大了肿瘤切除的成功率，提高了小鼠存活率 (" }, { "name": "xref", "data": { "text": "图2", "type": "fig", "rid": "F2", "data": [ { "name": "text", "data": "图2" } ] } }, { "name": "text", "data": "d)。" } ] }, { "name": "fig", "data": { "id": "F2", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图2" } ], "title": [ { "name": "text", "data": "（a）PTZ-TQ分子结构；（b）PTZ-TQ在THF和95%水含量THF/H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O中吸收光谱；（c）在808 nm激发下，PTZ-TQ在不同水含量（0%至95%）中的荧光强度；（d）NIR-II光学成像引导肿瘤切除的图示" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "23", "type": "bibr", "rid": "R23", "data": [ { "name": "text", "data": "23" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.2" } ], "title": [ { "name": "text", "data": "（a） Chemical formula of PTZ-TQ；（b） Absorption spectra of PTZ-TQ in tetrahydrofuran （THF） and in THF/H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O with 95% water volume fraction （" }, { "name": "italic", "data": [ { "name": "text", "data": "f" }, { "name": "sub", "data": [ { "name": "text", "data": "w" } ] } ] }, { "name": "text", "data": "）；（c） Emission of PTZ-TQ in THF/H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O （" }, { "name": "italic", "data": [ { "name": "text", "data": "f" }, { "name": "sub", "data": [ { "name": "text", "data": "w" } ] } ] }, { "name": "text", "data": "， 0% to 95%） under 808 nm excitation；（d） Illustration of the NIR-II optical imaging-guided tumor resection" }, { "name": "sup", "data": [ { "name": "text", "data": " ［" }, { "name": "xref", "data": { "text": "23", "type": "bibr", "rid": "R23", "data": [ { "name": "text", "data": "23" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481297&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481299&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481298&type=", "width": "140.10140991", "height": "73.74410248", "fontsize": "" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "Li团队" }, { "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": "，在BBTD两处反应位点引入多个基团，选用烷基噻吩(TA)-苯并双噻唑(B)-烷基噻吩(AT)和三苯胺(TPA)为转子，将双环二铜吡咯(DPP)单元嵌入，合成了一种新型的具有NIR-II发射的荧光分子TDADT (" }, { "name": "xref", "data": { "text": "图3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "图3" } ] } }, { "name": "text", "data": "a)。BBTD作为强电子受体，可以显著降低能带隙，红移吸收和发射波长。高度扭曲的AT–B–AT和TPA转子限制了分子间π-π相互作用增强了分子固体荧光，DPP基团具有良好的平面性和近红外(NIR)吸收性能与强电子受体BBTD偶联可以提高光吸收能力，这些使得TDADT的摩尔消光系数高达2.1×10" }, { "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": "(" }, { "name": "xref", "data": { "text": "图3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "图3" } ] } }, { "name": "text", "data": "b)。如" }, { "name": "xref", "data": { "text": "图3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "图3" } ] } }, { "name": "text", "data": "c所示，随着不良溶剂水含量的不断增加荧光逐渐增强，体现出典型的AIE性能。并且在水含量为90%时最大荧光波长达到1270 nm。通过纳米沉积法用DSPE-PEG" }, { "name": "sub", "data": [ { "name": "text", "data": "2000" } ] }, { "name": "text", "data": "封装的TDADT NPs具有良好的水分散性、生物相容性和胶束稳定性,其荧光量子产率Φ" }, { "name": "sub", "data": [ { "name": "text", "data": "f" } ] }, { "name": "text", "data": "=0.1%。基于TDADT NPs良好的体内NIR-II成像能力，选择腹膜癌病模型来评估TDADT NPs是否能鉴别和辅助切除超小肿瘤结节。首先通过表达荧光素酶(生物发光信号)的4T1 (4T1-luc)细胞构建腹膜癌小鼠，尾静脉注射TDADT NPs，如" }, { "name": "xref", "data": { "text": "图3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "图3" } ] } }, { "name": "text", "data": "d所示，12 h后观察到肿瘤的生物发光信号与NIR-II荧光信号完美重叠，说明TDADT NPs达到病灶处。首先对腹腔肿瘤进行肉眼观察的手术切除，术后在NIR-II荧光成像下仍能观察到大量残留的微小肿瘤，然后在TDADT NPs 的NIR-II图像引导下再次进行切除。第二次在NIR-II荧光成像引导下切除的肿瘤结节的直径明显小于第一次在肉眼下直接切除的肿瘤 (图" }, { "name": "xref", "data": { "text": "3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "3" } ] } }, { "name": "text", "data": "e、" }, { "name": "xref", "data": { "text": "3", "type": "fig", "rid": "F3", "data": [ { "name": "text", "data": "3" } ] } }, { "name": "text", "data": "f)。这些结果表明NIR-II AIE荧光成像引导手术能够切除超小肿瘤结节，很好的弥补了寻常手术肿瘤切除不完全这一缺点，同时也避免了对正常组织的伤害。" } ] }, { "name": "fig", "data": { "id": "F3", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图3" } ], "title": [ { "name": "text", "data": "（a）TDADT分子的结构；（b）THF和THF/H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O混合物中TDADT的摩尔消光系数（" }, { "name": "italic", "data": [ { "name": "text", "data": "f" }, { "name": "sub", "data": [ { "name": "text", "data": "w" } ] } ] }, { "name": "text", "data": "=95 %）；（c）THF/H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O混合物中荧光强度随水含量的变化图；（d）手术前后腹腔肿瘤的生物发光和NIR-II荧光成像数据（比例尺：4 mm）；（e）非引导组和图像引导组切除结节的生物发光和NIR-II成像（比例尺：5 mm）；（f）切除结节直径的统计数据" }, { "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": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.3" } ], "title": [ { "name": "text", "data": "（a）Chemical structure of TDADT；（b） Molar extinction coefficient of TDADT in THF and THF/H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O mixtures （" }, { "name": "italic", "data": [ { "name": "text", "data": "f" }, { "name": "sub", "data": [ { "name": "text", "data": "w" } ] } ] }, { "name": "text", "data": " = 95 %）；（c） Variation of photoluminescence （PL） intensity in THF/H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O mixtures with " }, { "name": "italic", "data": [ { "name": "text", "data": "f" }, { "name": "sub", "data": [ { "name": "text", "data": "w" } ] } ] }, { "name": "text", "data": "；（d） Imaging data for bioluminescence and NIR-II fluorescence of the tumor in abdominal cavity before and after surgery （scale bar： 4 mm）；（e） Bioluminescence and NIR-II imaging of resected nodules of unguided and image-guided groups （scale bar： 5 mm）；（f） Statistical data of nodules diameters resected " }, { "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": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481300&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481302&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481301&type=", "width": "136.95989990", "height": "96.04016876", "fontsize": "" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "上述工作中，NIR-II AIE纳米粒子是利用DSPE-PEG" }, { "name": "sub", "data": [ { "name": "text", "data": "3400" } ] }, { "name": "text", "data": "-NH" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "和DSPE-PEG" }, { "name": "sub", "data": [ { "name": "text", "data": "2000" } ] }, { "name": "text", "data": "这一类人工合成的封装基质制备的，这些纳米粒子存在的尺寸精确度控制较弱、体内的稳定性和生物相容性也有待进一步提高的缺点。因此，需要开发新的纳米粒子制备方法，以解决上述限制。Min" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "25", "type": "bibr", "rid": "R25", "data": [ { "name": "text", "data": "25" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "团队合成了以BBTD为受体，三苯胺为供体的D-A-D结构分子CH1 (" }, { "name": "xref", "data": { "text": "图4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "图4" } ] } }, { "name": "text", "data": "a)，其最大吸收波长达到700 nm (如" }, { "name": "xref", "data": { "text": "图4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "图4" } ] } }, { "name": "text", "data": "b)，并且最大发射波长超过900 nm (" }, { "name": "xref", "data": { "text": "图4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "图4" } ] } }, { "name": "text", "data": "c)，表现出NIR-II荧光性能。同时，还具有典型的AIE性能，如" }, { "name": "xref", "data": { "text": "图4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "图4" } ] } }, { "name": "text", "data": "d所示，随着不良溶剂水含量的增加，表现出聚集状态，荧光强度逐渐增强。采用一种蛋白质猿猴病毒40 (SV40)的病毒样颗粒(VLP)对CH1进行封装。相比于普遍使用的人工合成基质，这种蛋白质纳米笼具有高生物相容性、可控自组装、精确三维结构、空间可寻址性、负载能力、易于修改和可扩展制备等优点。合成的NIR-II纳米粒子CH1-SV40具有强荧光、高光稳定性和良好的生物相容性等优点，量子产率达到13.03%，可以实现高信噪比的成像引导手术。在肿瘤内注射CH1-SV40纳米粒子，对荷瘤小鼠进行NIR-II荧光成像。注射5 h后肿瘤部位的荧光强度依然非常高 (" }, { "name": "xref", "data": { "text": "图4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "图4" } ] } }, { "name": "text", "data": "e)。在NIR-II荧光指导下对肿瘤进行切除，术后未观察到肿瘤周围的正常组织呈现的荧光信号 (图" }, { "name": "xref", "data": { "text": "4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "4" } ] } }, { "name": "text", "data": "f、" }, { "name": "xref", "data": { "text": "4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "4" } ] } }, { "name": "text", "data": "g)，说明在NIR-II高分辨率和高可视化程度的荧光成像的指导下，可以准确的切除肿瘤，避免了不完全切除导致的癌症复发现象。并且可以看到荧光信号仅存在于肿瘤中 (图" }, { "name": "xref", "data": { "text": "4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "4" } ] } }, { "name": "text", "data": "h、" }, { "name": "xref", "data": { "text": "4", "type": "fig", "rid": "F4", "data": [ { "name": "text", "data": "4" } ] } }, { "name": "text", "data": "i)，表明其对肿瘤的特异靶向性。" } ] }, { "name": "fig", "data": { "id": "F4", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图4" } ], "title": [ { "name": "text", "data": "（a） CH1的分子结构；（b） CH1分子在甲苯、THF、DMSO和DMF中的紫外-可见吸收光谱；（c）CH1（25 μM）在各种溶剂中的荧光发射光谱（808 nm激发）。插图显示NIR-II荧光成像；（d）在DMSO和水的混合物中，CH1分子的荧光发射光谱；（e）注射的CH1-SV40（620 μM， 20 μL）在0-300 min在小鼠体内的分布；（f）和（g） CH1-SV40纳米粒子成像引导肿瘤切除后荷瘤小鼠的明场图像和NIR-II荧光图像，插图为切除的肿瘤；（h）和（i）分别在注射CH1-SV40纳米粒子的小鼠的心脏、肝脏、脾脏、内脏、肾脏、肺、胃和肿瘤组织中的CH1-SV40纳米粒子的离体明场和NIR-II荧光图像" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "25", "type": "bibr", "rid": "R25", "data": [ { "name": "text", "data": "25" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.4" } ], "title": [ { "name": "text", "data": "（a）Chemical structure of CH1；（b） UV-Vis absorption spectra of CH1 molecules in Toluene， THF， DMSO， and DMF respectively；（c） PL spectra of CH1 （25 μM） in various solvents after 808 nm excitation. The inset： NIR-II fluorescence imaging；（d） PL spectra of CH1 molecules excited at 808 nm in a mixture of DMSO and H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O；（e） Distribution of intratumor-injected CH1-SV40 （620 μM， 20 μL） in HeLa tumor-bearing mice during 0-300 min；（f） and （g） Bright field image and NIR-II fluorescence image of a HeLa tumor-bearing mouse following CH1-SV40 imaging-guided tumor removal， respectively. Insets show resected tumor；（h） and （i） Ex vivo bright-field and NIR-II fluorescence images of CH1-SV40 in the hearts， livers， spleens， guts， kidneys， lungs， stomachs， and tumor tissues of mice injected with CH1-SV40， respectively" }, { "name": "sup", "data": [ { "name": "text", "data": " ［" }, { "name": "xref", "data": { "text": "25", "type": "bibr", "rid": "R25", "data": [ { "name": "text", "data": "25" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481318&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481320&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481319&type=", "width": "96.74719238", "height": "60.97726822", "fontsize": "" } ] } } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2.2　NIR-II AIE材料在检测切除淋巴结手术中的应用" } ], "level": "2", "id": "s2b" } }, { "name": "p", "data": [ { "name": "text", "data": "淋巴系统在免疫系统中起着至关重要的作用，它能将淋巴运输到全身。当体内感染炎症或者是得癌症时都可能导致淋巴系统的紊乱" }, { "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": "。进行外科手术时，虽然将肿瘤切除了，但仍然有复发的可能性，其中部分原因是肿瘤会通过周围的淋巴结向远处转移，淋巴结(LNs)的引流与肿瘤的转移是密切相关的" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "27", "type": "bibr", "rid": "R27", "data": [ { "name": "text", "data": "27" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "，因此术前对LNs的检测是十分重要的。前哨淋巴结(SLN)是原发性肿瘤转移的第一个LN引流站，SLN成像为手术治疗安排提供了宝贵信息，在手术计划和术后治疗中起着很重要的作用" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "1", "type": "bibr", "rid": "R1", "data": [ { "name": "text", "data": "1" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "。Tang" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "28", "type": "bibr", "rid": "R28", "data": [ { "name": "text", "data": "28" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "的团队设计合成了一种新型“二合一”NIR-II AIE材料可用于对 SLN成像及切除。如" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "a所示，采用具有不同性质的电子供体，将以ACQ效应为主导的2TT-mC6B平面供体和具有AIE活性的2TT-oC6B扭曲供体相结合，并以BBTD为受体，形成新的分子2TT-m,oC6B。平面结构使2TT-m,oC6B在长波长范围内具有强烈的吸收，不仅能穿透深部组织，还能减少对活体的光损伤。在808 nm激光下摩尔吸收率达1.12 ×10" }, { "name": "sup", "data": [ { "name": "text", "data": "4" } ] }, { "name": "text", "data": " M" }, { "name": "sup", "data": [ { "name": "text", "data": "-1 " } ] }, { "name": "text", "data": "cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-1 " } ] }, { "name": "text", "data": "(" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "b),聚集态下其最大荧光波长达到1050 nm (" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "c)，扭曲的供体与三苯胺转子耦合可以有效限制聚集态分子内相互作用，表现出良好的AIE性能 (" }, { "name": "xref", "data": { "text": "图5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "图5" } ] } }, { "name": "text", "data": "d)。通过沉淀法制备的纳米粒子 2TT-m,oC6B NPs具有高稳定性以及良好的生物相容性，NIR-II量子产率高达3.7%。将2TT-m,oC6B NPs注射到裸鼠脚垫中，注射10 min后2TT-m,oC6B NPs迁移到淋巴血管，点亮SLN，2 h后SLN处荧光信号增强，出现在第二个淋巴结处，并且可以清晰的看到两个淋巴结之间的淋巴管，随着时间的推移，淋巴结内的荧光信号逐渐增强，并且在24 h时达到最大。在NIR-II AIE纳米粒子的荧光的引导下，直径小于1 mm的SLN被精确去除 (图" }, { "name": "xref", "data": { "text": "5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "5" } ] } }, { "name": "text", "data": "e-" }, { "name": "xref", "data": { "text": "5", "type": "fig", "rid": "F5", "data": [ { "name": "text", "data": "5" } ] } }, { "name": "text", "data": "j)，表明2TT-m,oC6B NPs可以很好的应用于小鼠体内对SLN的检测与切除。" } ] }, { "name": "fig", "data": { "id": "F5", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图5" } ], "title": [ { "name": "text", "data": "（a）2TT-m，oC6B分子结构；（b）聚集体中分子的摩尔吸收系数；（c）聚集体中分子的荧光光谱图；（d）不同的水含量下2TT-m，oC6B分子荧光强度；（e）小鼠明场图；（f-i）分别在10 min、2 h、4 h、24 h拍摄的荧光图像（比例尺：5 mm）；（j）NIR-II荧光图像引导下从小鼠提取的前哨淋巴结明场（左）和荧光（右）图（比例尺：2 mm）" }, { "name": "sup", "data": [ { "name": "text", "data": " ［" }, { "name": "xref", "data": { "text": "28", "type": "bibr", "rid": "R28", "data": [ { "name": "text", "data": "28" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.5" } ], "title": [ { "name": "text", "data": "（a）Chemical structure of 2TT-m，oC6B；（b） Molar absorption coefficient of molecules in aggregate；（c） Normalized PL spectra of molecules in aggregate；（d） PL spectra of 2TT-m，oC6B （10" }, { "name": "sup", "data": [ { "name": "text", "data": "-5" } ] }, { "name": "text", "data": " mol L" }, { "name": "sup", "data": [ { "name": "text", "data": "-1" } ] }, { "name": "text", "data": " ） in THF/H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O mixture with different " }, { "name": "italic", "data": [ { "name": "text", "data": "f" }, { "name": "sub", "data": [ { "name": "text", "data": "w" } ] } ] }, { "name": "text", "data": "；（e） Bright field；（f-i） Fluorescent field with images captured at 10 min， 2 h， 4 h， 24 h， respectively （scale bar： 5 mm）；（j） Bright （left） and fluorescent （right） images of sentinel lymph node extracted from the mouse under the guidance of NIR-II fluorescence （scale bar： 2 mm）" }, { "name": "sup", "data": [ { "name": "text", "data": " ［" }, { "name": "xref", "data": { "text": "28", "type": "bibr", "rid": "R28", "data": [ { "name": "text", "data": "28" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481321&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481323&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481322&type=", "width": "150.24441528", "height": "81.27864838", "fontsize": "" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "当然，除了对SLN的研究，其他肿瘤转移淋巴结的成像手术导航研究也很重要。Tian" }, { "name": "sup", "data": [ { "name": "text", "data": "[" }, { "name": "xref", "data": { "text": "29", "type": "bibr", "rid": "R29", "data": [ { "name": "text", "data": "29" } ] } }, { "name": "text", "data": "]" } ] }, { "name": "text", "data": "课题组以BBTD为受体两边分别引入香豆素(D1)和三苯胺(D2)作为供体，通过乙烯基将D2与四苯基乙烯相连以增加共轭长度，合成了一个具有典型AIE特性的NIR-II荧光分子A1，其分子结构如" }, { "name": "xref", "data": { "text": "图6", "type": "fig", "rid": "F6", "data": [ { "name": "text", "data": "图6" } ] } }, { "name": "text", "data": "a所示。A1分子的最大吸收波长达到780 nm左右(" }, { "name": "xref", "data": { "text": "图6", "type": "fig", "rid": "F6", "data": [ { "name": "text", "data": "图6" } ] } }, { "name": "text", "data": "b)，在水含量70%时最大发射波长超过1000 nm(" }, { "name": "xref", "data": { "text": "图6", "type": "fig", "rid": "F6", "data": [ { "name": "text", "data": "图6" } ] } }, { "name": "text", "data": "c)，并且D1和BBTD分子之间的乙烯基共轭桥加强了其摩尔吸收率 (ε=4.761×10" }, { "name": "sup", "data": [ { "name": "text", "data": "-4" } ] }, { "name": "text", "data": " M" }, { "name": "sup", "data": [ { "name": "text", "data": "-1 " } ] }, { "name": "text", "data": "cm" }, { "name": "sup", "data": [ { "name": "text", "data": "-1" } ] }, { "name": "text", "data": ")。利用沉淀法制备的A1 NPs具有良好的生物相容性，较高的绝对量子产率(1.23%)，同时还有很好的光热转换效率和活性氧生成能力，这些特性表明纳米粒子有可能进行多模式联合应用。在进行小鼠体内实验时，首先对小鼠注射荧光素酶表达的4T1 (4T1-luc)肿瘤细胞，当坐骨淋巴结和腋窝淋巴结观察生物发光信号后，通过监测生物发光成像(BLI)构建阳性淋巴结模型。在A1 NPs静脉注射24 h后观察到NIR-II荧光信号与BLI信号相匹配，在NIR-II图像引导下将荧光信号强的淋巴结和其他肿大的淋巴结一起切除，发现只有荧光信号明显增强的病灶为转移性淋巴结，其余肿大的淋巴结只有微弱荧光，没有生物发光信号，为非转移性淋巴结。这些数据表明A1 NPs能在术中准确识别转移性淋巴结，并指导手术切除，可以有效避免广泛清扫淋巴结导致的手术创伤型水肿现象 (" }, { "name": "xref", "data": { "text": "图6", "type": "fig", "rid": "F6", "data": [ { "name": "text", "data": "图6" } ] } }, { "name": "text", "data": "d-e)。" } ] }, { "name": "fig", "data": { "id": "F6", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图6" } ], "title": [ { "name": "text", "data": "（a） A1分子合成图；（b）不同浓度下A1在THF中的吸收曲线；（c）不同水含量下A1的荧光光谱；（d）生物发光成像（BLI）图像检测到原位乳腺癌小鼠坐骨淋巴结阳性；（e）阳性腋窝淋巴结的图像" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "29", "type": "bibr", "rid": "R29", "data": [ { "name": "text", "data": "29" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.6" } ], "title": [ { "name": "text", "data": "（a）Chemical structure of A1；（b） Absorption curves of A1 in THF at different concentrations；（c） PL spectra of A1 in THF/H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O mixture different " }, { "name": "italic", "data": [ { "name": "text", "data": "f" }, { "name": "sub", "data": [ { "name": "text", "data": "w" } ] } ] }, { "name": "text", "data": "；（d） BLI images detected a positive sciatic lymph node in orthotopic breast cancer mouse；（e） An identical set of images about positive axillary lymph node" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "xref", "data": { "text": "29", "type": "bibr", "rid": "R29", "data": [ { "name": "text", "data": "29" } ] } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481324&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481326&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481325&type=", "width": "141.03039551", "height": "88.94475555", "fontsize": "" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "尽管NIR-II荧光在手术导航中有许多优点，但其有一个最大的缺点是它必须依赖于NIR相机来检测信号，外科医生在进行手术时需要看着电脑屏幕。可见荧光虽然穿透性差，但引导手术中的优势在于它可以通过肉眼检测到，这将大大加快手术速度。在手术导航中，NIR-II荧光和可见荧光的结合，可以使互补优势最大化。因此，需要一种结合NIR-II荧光成像和可见荧光成像优点的导航模式。2022年Lin" }, { "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": "课题组利用了之前合成的分子TT3-oCB和DPBT (" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "a)，DPBT分子在可见光区具有荧光，其最大吸收波长达到450 nm (" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "b)，在水含量为90%时最大发射波长达到585 nm,并且表现出良好的AIE性能 (" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "c)" }, { "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": "，同时具有较高的荧光量子产率 (Φ" }, { "name": "sub", "data": [ { "name": "text", "data": "f" } ] }, { "name": "text", "data": "=56.4%)。而TT3-oCB分子最大吸收波长达到722 nm (" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "d),同时从50%水含量时开始荧光强度显著增强，最大发射波长超过1000 nm (" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "e)，是一个典型的NIR-II AIE分子" }, { "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": "。分别将TT3-oCB (NIR-II手术导航试剂)和DPBT (可见光手术导航试剂)制备成纳米粒子TT3-oCB NPs (Φ" }, { "name": "sub", "data": [ { "name": "text", "data": "f" } ] }, { "name": "text", "data": "=4.6%)和DPBT NPs，混合得到“鸡尾酒式”的AIE NPs。“鸡尾酒式”导航试剂不仅能在808 nm激光器激发下显示出NIR-II信号，还能在紫外灯下看见它的橙色荧光，极大发挥了这两种纳米粒子的优势。在进行大鼠实验时，将AIE NPs注入大鼠后肢足垫30 min后，在808 nm激光的激发下，NIR-II显像清晰地显示腹膜后的LNs和相应的淋巴管 (" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "f-i)，在明场下，将组织解剖并轻轻拉开 (" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "f-ii)，然后打开紫外线灯，可以通过肉眼观察到腹膜后LNs的可见荧光 (" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "f-iii)。在可见荧光的引导下，可以准确、完整地切除LNs。手术后，在可见荧光成像 (" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "f-v)和NIR-II荧光成像 (" }, { "name": "xref", "data": { "text": "图7", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图7" } ] } }, { "name": "text", "data": "f-vi)中均未发现残留的LNs组织。进一步表明“鸡尾酒式”的AIE NPs在引导LNs切除时既能快速定位LNs位置，又能通过肉眼进行手术，加快了手术速度，缩短了手术时间。" } ] }, { "name": "fig", "data": { "id": "F7", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图7" } ], "title": [ { "name": "text", "data": "（a） DPBT和TT3-oCB的分子结构式；（b） DPBT （10 μM）在不同水含量中的吸收光谱；（c）不同水含量下DPBT的荧光光谱；（d） TT3-oCB和TT3-oCB NPs的吸收光谱；（e）不同水含量下TT3-oCB的荧光光谱；（f）AIE NPs鸡尾酒引导大鼠腹膜后淋巴结的切除过程（比例尺：1 cm）" }, { "name": "sup", "data": [ { "name": "text", "data": " ［" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "30", "type": "bibr", "rid": "R30", "data": [ { "name": "text", "data": "30" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "32", "type": "bibr", "rid": "R32", "data": [ { "name": "text", "data": "32" } ] } } ], "rid": [ "R30", "R31", "R32" ], "text": "30-32", "type": "bibr" } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.8" } ], "title": [ { "name": "text", "data": "（a） Chemical structure of DPBT and TT3-oCB；（b） Absorption spectra of DPBT in acetone/water mixtures with different water fractions （" }, { "name": "italic", "data": [ { "name": "text", "data": "f" }, { "name": "sub", "data": [ { "name": "text", "data": "w" } ] } ] }, { "name": "text", "data": "）；（c） PL spectra of DPBT in acetone/water mixtures with different water fractions，［DPBT］ = 10 μM；（d） Absorption peak variation in solution （THF） and NPs （water）；（e） Variation of PL intensity with " }, { "name": "italic", "data": [ { "name": "text", "data": "f" }, { "name": "sub", "data": [ { "name": "text", "data": "w" } ] } ] }, { "name": "text", "data": " for TT3-oCB；（f） The resection process of the rat's retroperitoneal LNs guided by the AIE NPs cocktail （scale bar： 1 cm）" }, { "name": "sup", "data": [ { "name": "text", "data": " ［" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "30", "type": "bibr", "rid": "R30", "data": [ { "name": "text", "data": "30" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "32", "type": "bibr", "rid": "R32", "data": [ { "name": "text", "data": "32" } ] } } ], "rid": [ "R30", "R31", "R32" ], "text": "30-32", "type": "bibr" } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481327&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481329&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481328&type=", "width": "158.79977417", "height": "60.36016083", "fontsize": "" } ] } } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "2.3　NIR-II AIE材料在其他手术中的应用" } ], "level": "2", "id": "s2c" } }, { "name": "p", "data": [ { "name": "text", "data": "NIR-II AIE材料的手术导航作用不仅能应用于肿瘤、淋巴结类疾病，对其他疾病的术前诊断，术中" } ] }, { "name": "p", "data": [ { "name": "text", "data": "辅助和术后评估也有显著的效果。Tang的团队以烷基噻吩(T)作供体，BBTD作为受体，TPA作扭转转子和第二供体基团制备了一个D′-D-A-D-D′型染料" }, { "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": "。在之前的基础上，通过改变噻吩上己基的取代位置，实现结构异构化，成功合成了一个可以用于术中识别输尿管的纳米粒子2TT-oC6B NPs (Φ" }, { "name": "sub", "data": [ { "name": "text", "data": "f" } ] }, { "name": "text", "data": "=11%)，其小分子2TT-oC6B结构如" }, { "name": "xref", "data": { "text": "图8", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图8" } ] } }, { "name": "text", "data": "a所示。该分子具有314 nm的大斯托克斯位移 (" }, { "name": "xref", "data": { "text": "图8", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图8" } ] } }, { "name": "text", "data": "b)，从水含量为50%开始荧光强度随着水含量的增加显著增强，在水含量为90%时其荧光强度约为0%时的6倍 (" }, { "name": "xref", "data": { "text": "图8", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图8" } ] } }, { "name": "text", "data": "c)。利用DSPE-PEG" }, { "name": "sub", "data": [ { "name": "text", "data": "2000 " } ] }, { "name": "text", "data": "将其制备成纳米粒子2TT-oC6B NPs，2TT-oC6B NPs具有良好的稳定性。在进行活体实验时，逆行注射2TT-oC6B NPs到兔的输尿管，对于完全渗漏的病例，逆行注射的2TT-oC6B NPs只能到达输尿管渗漏点，并迅速渗漏到周围组织器官，在4 s内发出大面积荧光信号；对于部分泄漏病例，2TT-oC6B NPs泄漏的速度要慢得多，仅在4 s内出现一个亮点如" }, { "name": "xref", "data": { "text": "图8", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图8" } ] } }, { "name": "text", "data": "d所示。因此，利用这些高亮度的NIR-II AIE纳米材料可以初步判断输尿管损伤程度，为后续修复提供指导。2TT-oC6B NPs也能评估输尿管修复的成功程度，如" }, { "name": "xref", "data": { "text": "图8", "type": "fig", "rid": "F7", "data": [ { "name": "text", "data": "图8" } ] } }, { "name": "text", "data": "e，在输尿管损伤修复后，逆行注射的2TT-oC6B NPs可以顺利通过渗漏部位而不会进一步渗漏，验证了输尿管再通成功。以上结果表明2TT-oC6B NPs能够通过其高亮荧光快速判断输尿管损伤，准确定位输尿管内异常部位，减少手术过程中输尿管损伤" }, { "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": "。" } ] }, { "name": "fig", "data": { "id": "F8", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图8" } ], "title": [ { "name": "text", "data": "（a） 2TT-mC6B和2TT-oC6B的结构示意图；（b）分子在THF中的吸收和发射光谱；（c）不同水含量的α" }, { "name": "sub", "data": [ { "name": "text", "data": "AIE" } ] }, { "name": "text", "data": "曲线；（d）输尿管完全和部分漏尿兔逆行注射2TT-oC6B纳米粒子后不同时间点的荧光显像。红色箭头表示输尿管漏的位置；（e）输尿管损伤修复前后的荧光成像。红色箭头表示输尿管漏的位置（比例尺：1 cm）" }, { "name": "sup", "data": [ { "name": "text", "data": " ［" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "33", "type": "bibr", "rid": "R33", "data": [ { "name": "text", "data": "33" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "34", "type": "bibr", "rid": "R34", "data": [ { "name": "text", "data": "34" } ] } } ], "rid": [ "R33", "R34" ], "text": "33-34", "type": "bibr" } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.8" } ], "title": [ { "name": "text", "data": "（a） Chemical structure of 2TT-mC6B and 2TT-oC6B；（b） Absorption and emission spectra in THF；（c） α" }, { "name": "sub", "data": [ { "name": "text", "data": "AIE" } ] }, { "name": "text", "data": " curves with water fraction；（d） Fluorescence imaging at various time points as indicated after retrograde injection of 2TT-oC6B NPs in rabbits with complete and partial leakage of the ureter. The red arrows denote the location of ureteral leakage；（e） Fluorescence imaging of the ureter before and after the repair of ureteral injury. The red arrows denote the location of ureteral leakage （scale bar： 1 cm）" }, { "name": "sup", "data": [ { "name": "text", "data": " ［" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "33", "type": "bibr", "rid": "R33", "data": [ { "name": "text", "data": "33" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "34", "type": "bibr", "rid": "R34", "data": [ { "name": "text", "data": "34" } ] } } ], "rid": [ "R33", "R34" ], "text": "33-34", "type": "bibr" } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481330&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481332&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481331&type=", "width": "148.44595337", "height": "106.55331421", "fontsize": "" } ] } }, { "name": "p", "data": [ { "name": "text", "data": "Tang的团队利用N，N-二苯基萘-1-胺（BPN）作供体，BBTD作受体合成新型小分子BPN-BBTD其分子结构如" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "a" }, { "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": "，最大吸收波长达到700 nm，并且荧光发射波长达949 nm (如" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "b)。如" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "c所示从水含量为30%开始荧光强度显著增强表现出典型的AIE性能。使用纳米沉淀法制备成BPN-BBTD NPs，其具有良好的光稳定性、低毒性和优异的生物相容性，并且在NIR-Ⅱ展现出较高的荧光量子产率(Φ" }, { "name": "sub", "data": [ { "name": "text", "data": "f" } ] }, { "name": "text", "data": "=1.8%)，可用于体内 NIR-Ⅱ生物医学成像。BPN-BBTD NPs作为荧光剂，在进行活体实验时，在严重病变的肠段具有强烈NIR-II荧光信号 (" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "d-i)，然后手术切除具有强NIR-II荧光信号的结肠段 (" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "d-ii)。切除后，只在剩余结肠观察到微弱的NIR-II荧光信号。最后，将前侧(" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "d-iii)和后侧 (" }, { "name": "xref", "data": { "text": "图9", "type": "fig", "rid": "F9", "data": [ { "name": "text", "data": "图9" } ] } }, { "name": "text", "data": "d-iv)肠断分别进行缝合。结果表明BPN-BBTD NPs用于手术导航可以精确定位炎症性肠病(IBD)模型中的病变肠段，进行可视化的切除严重炎症性肠断，提高炎症肠切除术的准确性并在一定程度上减少并发症" }, { "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": "。" } ] }, { "name": "fig", "data": { "id": "F9", "caption": [ { "lang": "zh", "label": [ { "name": "text", "data": "图9" } ], "title": [ { "name": "text", "data": "（a） BPN-BBTD的结构示意图；（b） BPN-BBTD 的紫外和荧光图；（c）化合物BPN-BBTD的荧光强度与THF/H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O混合物的水含量的关系图。I" }, { "name": "sub", "data": [ { "name": "text", "data": "0" } ] }, { "name": "text", "data": "和I分别是BPN-BBTD在纯THF和不同水含量中的荧光强度；（d-i）在793 nm激光激发下，NIR-II荧光准确定位炎症肠段；（d-ii）进行肠切除术；（d-iii）前侧的吻合过程；以及（d-iv）后侧的吻合过程（比例尺：1 cm；浅蓝色箭头：病变肠段）" }, { "name": "sup", "data": [ { "name": "text", "data": "［" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "35", "type": "bibr", "rid": "R35", "data": [ { "name": "text", "data": "35" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "36", "type": "bibr", "rid": "R36", "data": [ { "name": "text", "data": "36" } ] } } ], "rid": [ "R35", "R36" ], "text": "35-36", "type": "bibr" } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "。" } ] }, { "lang": "en", "label": [ { "name": "text", "data": "Fig.9" } ], "title": [ { "name": "text", "data": "（a） Chemical structure of BPN-BBTD；（b） Absorption and PL spectra of BPN-BBTD in chloroform；（c） Plot of the PL peak intensity of compound BPN-BBTD and the " }, { "name": "italic", "data": [ { "name": "text", "data": "f" }, { "name": "sub", "data": [ { "name": "text", "data": "w" } ] } ] }, { "name": "text", "data": " of the THF/H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O mixture. I" }, { "name": "sub", "data": [ { "name": "text", "data": "0" } ] }, { "name": "text", "data": " and I are the PL peak intensities of BPN-BBTD AIEgen in pure THF （" }, { "name": "italic", "data": [ { "name": "text", "data": "f" }, { "name": "sub", "data": [ { "name": "text", "data": "w" } ] } ] }, { "name": "text", "data": " = 0%） and THF/H" }, { "name": "sub", "data": [ { "name": "text", "data": "2" } ] }, { "name": "text", "data": "O mixtures with specific" }, { "name": "italic", "data": [ { "name": "text", "data": " f" }, { "name": "sub", "data": [ { "name": "text", "data": "w" } ] } ] }, { "name": "text", "data": "， respectively；（d-i） The accurately located intestinal segment with strong NIR-II fluorescence under 793 nm laser excitation；（d-ii） intestinal resection；（d-iii） the anastomosis process on the anterior side；（d-iv） the anastomosis process on the posterior side （scale bar： 1 cm； light blue arrow： the diseased intestinal segment）" }, { "name": "sup", "data": [ { "name": "text", "data": " ［" }, { "name": "blockXref", "data": { "data": [ { "name": "xref", "data": { "text": "35", "type": "bibr", "rid": "R35", "data": [ { "name": "text", "data": "35" } ] } }, { "name": "text", "data": "-" }, { "name": "xref", "data": { "text": "36", "type": "bibr", "rid": "R36", "data": [ { "name": "text", "data": "36" } ] } } ], "rid": [ "R35", "R36" ], "text": "35-36", "type": "bibr" } }, { "name": "text", "data": "］" } ] }, { "name": "text", "data": "." } ] } ], "subcaption": [], "note": [], "graphics": [ { "print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481333&type=", "small": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481335&type=", "big": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=39481334&type=", "width": "141.40768433", "height": "109.35620117", "fontsize": "" } ] } } ] } ] }, { "name": "sec", "data": [ { "name": "sectitle", "data": { "title": [ { "name": "text", "data": "3　总　　结" } ], "level": "1", "id": "s3" } }, { "name": "p", "data": [ { "name": "text", "data": "近年来，随着新型NIR-II AIE荧光探针的发展，已经开发了很多NIR-II荧光材料，就已经开发的NIR-II AIE材料而言，大部分分子是D-A-D结构，在这些分子中通常以强缺电性的BBTD类化合物为受体，引入强供电子基团和转子增强分子扭曲度和共轭长度，使分子发射波长红移到NIR-II。同时，文献中报道的NIR-II AIE荧光探针大部分用于肿瘤和淋巴结的检测切除，基于NIR-II的高分辨率、低自体荧光干扰性和深度穿透性等良好的性能，用于手术导航可以使医生快速可视化定位患病区域，很大程度提高了微小肿瘤结节的切除率并且准确区分正常组织与患病组织，减少了对正常组织的伤害，提高了手术准确率。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "但是，NIR-II AIE荧光探针仍然有很大的发展空间。1）由于目前已报道的分子大多是D-A-D结构，同时分子受体基团过于单一，因此，需要设计合成新的结构的NIR-II AIE分子并且加强开发新型受体基团。通过调节分子结构红移发射波长、提高量子产率以调节分子性能；2）提高NIR-II AIE纳米材料靶向性，目前文献中报道的大多数病例，由于高渗透长滞留效应，主要通过被动靶向实现NIR-II AIE纳米探针在病灶区域的积累，为了实现更精确的标记，不能仅仅依靠增强通透性和保留效应，而是要依靠更有效的靶向策略。一方面，外源荧光物质可能在肿瘤中积累，通过特定的靶向策略进一步提高信噪比，同时减少在正常组织中的沉积，从而降低毒性作用。此外，由于肿瘤的异质性，单靶点分子探针仍然存在低信噪比和高假阳性率。因此，开发具有多个特异性靶点和更强亲和力的NIR-II AIE材料，可能是未来一个可行的研究方向；3）开发成像治疗一体化的荧光试剂, 单一模式的成像或者治疗通常不能同时实现药物和肿瘤组织信息的精确定位。与传统的治疗方法相比，图像引导的治疗能够实现更精确的癌症治疗，极大地提高了疾病治疗的精准性和有效性，开发具有多种诊断成像和协同治疗功能的多功能光治疗剂，仍然是一项极具挑战性的任务。总之，开发更多NIR-II AIE探针并且深度探索他们的应用，不仅仅是手术导航上的应用，将会使其在各个领域焕发不同的生机。" } ] }, { "name": "p", "data": [ { "name": "text", "data": "本文（补充文件及）专家审稿意见和作者回复内容下载地址：" }, { "name": "extlink", "data": { "text": [ { "name": "text", "data": "http://cjl.lightpublishing.cn/thesisDetails#10.37188/CJL.20220" } ], "href": "http://cjl.lightpublishing.cn/thesisDetails#10.37188/CJL.20220" } }, { "name": "text", "data": "***（20220***为文章稿号）." } ] } ] } ], "footnote": [], "reflist": { "title": [ { "name": "text", "data": "参考文献" } ], "data": [ { "id": "R1", "label": "1", "citation": [ { "lang": "en", "text": [ { "name": "text", "data": "YANG R Q" }, { "name": "text", "data": "， " }, { "name": "text", "data": "LOU K L" }, { "name": "text", "data": "， " }, { "name": "text", "data": "WANG P Y" }, { "name": "text", "data": "， " }, { "name": "text", "data": "et al" }, { "name": "text", "data": ". 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