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Progress on Aggregation-induced Emission Probes for Mitochondria Target and Cancer Cell Identification
Invited Paper | Updated：2021-03-19
|
Progress on Aggregation-induced Emission Probes for Mitochondria Target and Cancer Cell Identification
- Chinese Journal of Luminescence Vol.42, Issue 3, (2021)
- Affiliations：College of Chemistry and Materials Science, Jinan University,Guangzhou,China,510632;State Key Laboratory of Luminescent Materials and Devices, Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, SCUT-HKUST Joint Research Institute, South China University of Technology,Guangzhou,China,510640;Department of Chemistry, Hong Kong Branch of Chinese National Engineering Research Center for Tissue Restoration and Reconstruction, The Hong Kong University of Science and Technology,Hong Kong,China,999077
- Author bio：
- Funds：National Natural Science Foundation of China(21905113;21788102;51620105009);Natural Science Foundation of Guangdong Province(2020A1515010622;2019B030301003;2016A030312002);Innovation and Technology Commission of Hong Kong(ITC-CNERC14S01);Fundamental Research Funds for the Central Universities(21619316)
- DOI：10.37188/CJL.20200351 CLC： O482.31
Published：01 March 2021，
Received：15 November 2020，
Revised：05 December 2020，
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Cite this article
Jia-qi PENG, Ming CHEN, An-jun QIN, et al. Progress on Aggregation-induced Emission Probes for Mitochondria Target and Cancer Cell Identification. [J]. Chinese Journal of Luminescence 42(3):348-360(2021)
Jia-qi PENG, Ming CHEN, An-jun QIN, et al. Progress on Aggregation-induced Emission Probes for Mitochondria Target and Cancer Cell Identification. [J]. Chinese Journal of Luminescence 42(3):348-360(2021) DOI： 10.37188/CJL.20200351.
Progress on Aggregation-induced Emission Probes for Mitochondria Target and Cancer Cell Identification
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"text": "3",
"type": "bibr",
"rid": "R3",
"data": [
{
"name": "text",
"data": "3"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "6",
"type": "bibr",
"rid": "R6",
"data": [
{
"name": "text",
"data": "6"
}
]
}
}
],
"rid": [
"R3",
"R4",
"R5",
"R6"
],
"text": "3-6",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。"
}
]
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "相比而言，荧光成像具有灵敏度高、发射光谱多样性、无创性、时空分辨率高、扫描速度快和实时监控等优点"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "7",
"type": "bibr",
"rid": "R7",
"data": [
{
"name": "text",
"data": "7"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "9",
"type": "bibr",
"rid": "R9",
"data": [
{
"name": "text",
"data": "9"
}
]
}
}
],
"rid": [
"R7",
"R8",
"R9"
],
"text": "7-9",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "，因此被广泛应用于生物学和医学等众多领域的研究。近年来，荧光成像在癌症诊断中备受关注。而荧光染料则是荧光成像的核心。由于传统的荧光染料具有聚集促使荧光猝灭(Aggregation-caused quenching，ACQ)效应，它们只能在极低的浓度下使用，从而使其在成像时易受激发光刺激产生光漂白"
},
{
"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": "11",
"type": "bibr",
"rid": "R11",
"data": [
{
"name": "text",
"data": "11"
}
]
}
}
],
"rid": [
"R10",
"R11"
],
"text": "10-11",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。传统荧光染料的这一缺陷严重限制了它们的超灵敏度分析和长期追踪成像能力，阻碍了其在肿瘤成像中的应用。2001年，Tang课题组提出了聚集诱导发光(Aggregation-induced emission，AIE)概念"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "12",
"type": "bibr",
"rid": "R12",
"data": [
{
"name": "text",
"data": "12"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。不同于ACQ分子，AIE荧光分子具有螺旋桨结构和灵活的分子构型，它们易在溶液中由于分子内运动使得激子猝灭，从而不发光或只发射微弱的荧光；而在聚集状态下由于分子内运动受限，非辐射跃迁被抑制从而实现荧光增强"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "13",
"type": "bibr",
"rid": "R13",
"data": [
{
"name": "text",
"data": "13"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "17",
"type": "bibr",
"rid": "R17",
"data": [
{
"name": "text",
"data": "17"
}
]
}
}
],
"rid": [
"R13",
"R14",
"R15",
"R16",
"R17"
],
"text": "13-17",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。AIE分子这种“越聚集越亮”的性质使其能在高浓度下发挥作用，且具有出色的灵敏度和光稳定性，从而有望用于生物长期示踪分析识别和成像"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "18",
"type": "bibr",
"rid": "R18",
"data": [
{
"name": "text",
"data": "18"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "21",
"type": "bibr",
"rid": "R21",
"data": [
{
"name": "text",
"data": "21"
}
]
}
}
],
"rid": [
"R18",
"R19",
"R20",
"R21"
],
"text": "18-21",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。"
}
]
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "目前，科学家们通常用荧光分子或纳米粒子对肿瘤细胞的特异性标记物进行标靶来提高荧光染料对癌细胞的特异性识别"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "22",
"type": "bibr",
"rid": "R22",
"data": [
{
"name": "text",
"data": "22"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "23",
"type": "bibr",
"rid": "R23",
"data": [
{
"name": "text",
"data": "23"
}
]
}
}
],
"rid": [
"R22",
"R23"
],
"text": "22-23",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。虽然该方法可以提高探针对癌细胞和正常细胞成像的对比度，但探针染料设计、制备和纯化过程均较为复杂，且无法诊断多种癌细胞系，因此不具有普适性。而线粒体作为细胞的能量工厂，在癌细胞和正常细胞中都是必不可少的。事实上，癌细胞与正常细胞的线粒体之间存在许多显著差异(包括细胞器大小、数量和形状、蛋白质合成速率和细胞器周转率、以及线粒体内膜的多肽和脂质分布等的不一致)"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "24",
"type": "bibr",
"rid": "R24",
"data": [
{
"name": "text",
"data": "24"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "28",
"type": "bibr",
"rid": "R28",
"data": [
{
"name": "text",
"data": "28"
}
]
}
}
],
"rid": [
"R24",
"R25",
"R26",
"R27",
"R28"
],
"text": "24-28",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "；此外，癌细胞中线粒体的膜电位相比于正常细胞中也会出现显著提高"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "29",
"type": "bibr",
"rid": "R29",
"data": [
{
"name": "text",
"data": "29"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "31",
"type": "bibr",
"rid": "R31",
"data": [
{
"name": "text",
"data": "31"
}
]
}
}
],
"rid": [
"R29",
"R30",
"R31"
],
"text": "29-31",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。因此，根据这些差异性设定一类识别癌细胞的通用靶标十分具有可靠性。本文对可用于特异性线粒体成像和癌细胞识别的AIE荧光探针从设计原理、成像应用和机理研究三个方面进行系统概括和总结，并对其未来的发展方向作出了展望。"
}
]
}
]
},
{
"name": "sec",
"data": [
{
"name": "sectitle",
"data": {
"title": [
{
"name": "text",
"data": "2 荧光探针的设计原理"
}
],
"level": "1",
"id": "s2"
}
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "可特异性标记线粒体的荧光探针的设计原理主要有在AIE分子上引入带正电荷基团、主体-客体超分子相互作用以及制备表面修饰线粒体靶向基团的纳米材料。"
}
]
},
{
"name": "sec",
"data": [
{
"name": "sectitle",
"data": {
"title": [
{
"name": "text",
"data": "2.1 引入带正电荷基团"
}
],
"level": "2",
"id": "s2a"
}
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "线粒体的膜电位差容易吸引带正电荷的分子富集在其内部。基于带正电荷基团的AIE分子一方面具有较好水溶性，增加其和细胞的相互作用；另一方面能够优先靶向细胞的线粒体，并实现荧光成像。目前，常见的用于修饰AIE分子的正电荷基团主要有三苯基膦盐(TPP)、吡啶及吡啶衍生物盐和花菁盐等"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "32",
"type": "bibr",
"rid": "R32",
"data": [
{
"name": "text",
"data": "32"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "37",
"type": "bibr",
"rid": "R37",
"data": [
{
"name": "text",
"data": "37"
}
]
}
}
],
"rid": [
"R32",
"R33",
"R34",
"R35",
"R36",
"R37"
],
"text": "32-37",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "("
},
{
"name": "xref",
"data": {
"text": "图1",
"type": "fig",
"rid": "F1",
"data": [
{
"name": "text",
"data": "图1"
}
]
}
},
{
"name": "text",
"data": ")。2013年，Tang等"
},
{
"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": " 使用TPP对四苯乙烯(TPE)进行功能化修饰得到了AIE分子TPE-TPP("
},
{
"name": "xref",
"data": {
"text": "图2",
"type": "fig",
"rid": "F2",
"data": [
{
"name": "text",
"data": "图2"
}
]
}
},
{
"name": "text",
"data": ")。TPP通过其带正电荷和亲脂性促进分子探针进入线粒体，从而使TPE-TPP可以特异性靶向细胞线粒体。线粒体的微环境限制了TPE-TPP激发后的分子运动，从而使其发射荧光信号。这种成像信号相比于传统的商业化染料如Mito Tracker具有更优异的稳定性，展示了AIE荧光探针可用于长期细胞器示踪成像的优势。尽管如此，TPE-TPP分子中的TPE和TPP单元之间通过亚甲基进行间隔，导致TPP并不能对TPE产生电子效应，从而使TPE-TPP的发射仅源自于TPE的蓝光。"
}
]
},
{
"name": "fig",
"data": {
"id": "F1",
"caption": [
{
"lang": "zh",
"label": [
{
"name": "text",
"data": "图1"
}
],
"title": [
{
"name": "text",
"data": "线粒体靶向带正电荷AIE探针设计示意图"
}
]
},
{
"lang": "en",
"label": [
{
"name": "text",
"data": "Fig.1"
}
],
"title": [
{
"name": "text",
"data": "Schematic diagram of designing mitochondria-targeted AIE probes bearing positive charge groups"
}
]
}
],
"subcaption": [],
"note": [],
"graphics": [
{
"print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21348741&type=",
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"data": {
"id": "F2",
"caption": [
{
"lang": "zh",
"label": [
{
"name": "text",
"data": "图2"
}
],
"title": [
{
"name": "text",
"data": "几种常见AIE探针的分子结构及其线粒体靶向成像(右图内标尺为20 μm)"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "34",
"type": "bibr",
"rid": "R34",
"data": [
{
"name": "text",
"data": "34"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
}
]
},
{
"lang": "en",
"label": [
{
"name": "text",
"data": "Fig.2"
}
],
"title": [
{
"name": "text",
"data": "Molecular structures of several AIE probes and their mitochondria-targeted imaging. The bar in right pictures is 20 μm"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "34",
"type": "bibr",
"rid": "R34",
"data": [
{
"name": "text",
"data": "34"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
}
]
}
],
"subcaption": [],
"note": [],
"graphics": [
{
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]
}
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "相比而言，具有长吸收和发射波长的荧光探针在减少激发光对组织的光损伤和避免生物自荧光等方面具有显著的优势，因而备受科研工作者的关注"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "38",
"type": "bibr",
"rid": "R38",
"data": [
{
"name": "text",
"data": "38"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "39",
"type": "bibr",
"rid": "R39",
"data": [
{
"name": "text",
"data": "39"
}
]
}
}
],
"rid": [
"R38",
"R39"
],
"text": "38-39",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。Tang等"
},
{
"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": "合成了TPE苯环直接含有吡啶盐衍生物修饰的AIE化合物TPE-IQ("
},
{
"name": "xref",
"data": {
"text": "图2",
"type": "fig",
"rid": "F2",
"data": [
{
"name": "text",
"data": "图2"
}
]
}
},
{
"name": "text",
"data": ")。TPE-IQ中的吡啶盐是强吸电子基团，而TPE中的三苯乙烯部分具有弱的给电子性。这种弱的给受体(D-A)效应诱使TPE-IQ发射绿光，且其可用于高选择性的、点亮线粒体的荧光探针。Tang等"
},
{
"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": "还通过在三苯乙烯单元上修饰给电子甲氧基，增强了D-A效应，获得了线粒体AIE探针TPE-IQ-2O("
},
{
"name": "xref",
"data": {
"text": "图2",
"type": "fig",
"rid": "F2",
"data": [
{
"name": "text",
"data": "图2"
}
]
}
},
{
"name": "text",
"data": ")。TPE-IQ-2O在可见光区430 nm处有最大吸收峰。此外，相比于TPE-IQ，TPE-IQ-2O能够发射较红的黄色荧光。"
}
]
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "通过在电子给受体间引入共轭π桥构建D-π-A结构，将有利于增强分子内电荷转移(ICT)效应并使化合物的发光波长红移。Tang等"
},
{
"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": "通过在TPE单元和吡啶盐单元之间键接双键得到了D-π-A结构的AIE化合物TPE-Py("
},
{
"name": "xref",
"data": {
"text": "图2",
"type": "fig",
"rid": "F2",
"data": [
{
"name": "text",
"data": "图2"
}
]
}
},
{
"name": "text",
"data": ")。TPE-Py中的双键能够有效增加分子共轭，促进ICT效应，使化合物发射黄光。 此外，TPE-Py和TPE-IQ-2O具有类似的发光波长，说明调节电子给受体的电子效应和增加π桥同样能对分子的发光波长产生影响。作者进一步研究发现，得益于TPE-Py兼具亲脂性和阳离子性，其能对活细胞中的线粒体进行特异性靶向荧光标记。花菁盐是构建近红外花菁类染料常用的电子受体基团。Tang等"
},
{
"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": "进而在TPE上修饰花菁盐得到了AIE化合物TPE-Ph-In("
},
{
"name": "xref",
"data": {
"text": "图2",
"type": "fig",
"rid": "F2",
"data": [
{
"name": "text",
"data": "图2"
}
]
}
},
{
"name": "text",
"data": ")。TPE-Ph-In相比于TPE-Py，分子内除含有更强的电子受体之外，其给受体间的共轭π桥也更长，因此能够发射670 nm的深红光。此外，基于TPE-Ph-In强的ICT效应，其具有较大的斯托克斯位移(约225 nm)，因此能够有效避免传统荧光染料存在的发射光自吸收问题。同时得益于红光材料的成像优势，其能够用于特异性靶向线粒体的高光稳定性和高分辨率的荧光探针。"
}
]
}
]
},
{
"name": "sec",
"data": [
{
"name": "sectitle",
"data": {
"title": [
{
"name": "text",
"data": "2.2 主体-客体超分子相互作用"
}
],
"level": "2",
"id": "s2b"
}
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "主客体化学在超分子自组装和荧光识别等方面具有显著发展优势"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "40",
"type": "bibr",
"rid": "R40",
"data": [
{
"name": "text",
"data": "40"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "42",
"type": "bibr",
"rid": "R42",
"data": [
{
"name": "text",
"data": "42"
}
]
}
}
],
"rid": [
"R40",
"R41",
"R42"
],
"text": "40-42",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。主体-客体分子间的主客体相互作用主要由氢键、亲疏水作用和金属-配体配位等驱动产生"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "43",
"type": "bibr",
"rid": "R43",
"data": [
{
"name": "text",
"data": "43"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "44",
"type": "bibr",
"rid": "R44",
"data": [
{
"name": "text",
"data": "44"
}
]
}
}
],
"rid": [
"R43",
"R44"
],
"text": "43-44",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。最近，Tang等"
},
{
"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": "首次报道了通过主体-客体相互作用来构建线粒体成像荧光探针。作者通过在TPE上修饰不同数目的吡啶盐基团合成了一系列AIE化合物TPE-2EP、TPE-3EP和TPE-4EP。这3种AIE分子具有良好水溶性和较红(约600 nm)的发光波长。此外，葫芦[n]脲是一类理想的大环宿主分子，其疏水腔可以和各种大小、形状的客体分子互补结合，形成具有良好生物相容性的组装体"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "46",
"type": "bibr",
"rid": "R46",
"data": [
{
"name": "text",
"data": "46"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "49",
"type": "bibr",
"rid": "R49",
"data": [
{
"name": "text",
"data": "49"
}
]
}
}
],
"rid": [
"R46",
"R47",
"R48",
"R49"
],
"text": "46-49",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。在此基础上，作者通过协调主客体之间相互作用，将TPE-2EP、TPE-3EP和TPE-4EP分别与葫芦[8]脲组装，形成了3种尺寸和形状(球形或立方形)不一的纳米级超分子组装体TPE-2EP@CB[8]"
},
{
"name": "text",
"data": "、TPE-3EP@CB[8]和TPE-4EP@CB[8]"
},
{
"name": "text",
"data": "("
},
{
"name": "xref",
"data": {
"text": "图3",
"type": "fig",
"rid": "F3",
"data": [
{
"name": "text",
"data": "图3"
}
]
}
},
{
"name": "text",
"data": ")"
},
{
"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": "。葫芦[8]脲的疏水空腔不仅提供了容纳AIE分子吡啶盐支链的空间，而且使分子在激发之后的构型松弛被抑制，从而使组装体发射强荧光。此外，这些组装体的发光行为还受化合物中吡啶盐的数量影响。例如，三吡啶盐化合物TPE-3EP和葫芦[8]"
},
{
"name": "text",
"data": "脲形成的组装体发光效率最高，且相比于其溶液态荧光增强最为显著。这些组装体可实现对细胞溶酶体和线粒体的双重成像。不同于先前报道的小分子荧光探针，这种组装体将通过内吞的方式进入细胞，进而富集在细胞器内。而组装体内部或表面存在的吡啶盐基团依然是诱导其进入线粒体的动因。因此，这项研究提供了一种新型构建细胞器成像试剂的方式。"
}
]
},
{
"name": "fig",
"data": {
"id": "F3",
"caption": [
{
"lang": "zh",
"label": [
{
"name": "text",
"data": "图3"
}
],
"title": [
{
"name": "text",
"data": "通过主客体相互作用构建线粒体成像荧光探针示意图"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "45",
"type": "bibr",
"rid": "R45",
"data": [
{
"name": "text",
"data": "45"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
}
]
},
{
"lang": "en",
"label": [
{
"name": "text",
"data": "Fig.3"
}
],
"title": [
{
"name": "text",
"data": "Schematic diagram of constructing mitochondria-targeted fluorescent probes with host-guest interaction"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "45",
"type": "bibr",
"rid": "R45",
"data": [
{
"name": "text",
"data": "45"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
}
]
}
],
"subcaption": [],
"note": [],
"graphics": [
{
"print": "http://html.publish.founderss.cn/rc-pub/api/common/picture?pictureId=21348764&type=",
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},
{
"name": "sec",
"data": [
{
"name": "sectitle",
"data": {
"title": [
{
"name": "text",
"data": "2.3 表面修饰线粒体靶向基团的纳米材料"
}
],
"level": "2",
"id": "s2c"
}
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "AIE纳米材料由于其高发光效率和极佳的抗光漂白性在荧光成像领域受到了越来越多的关注。2016年，《自然》杂志评价AIE点(即AIE纳米材料)和量子点、半导体聚合物点以及上转化纳米粒子是当今4种重要的生物纳米成像材料"
},
{
"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": "。AIE纳米材料通常通过两亲性分子包裹AIE分子来制备。相比于小分子荧光探针，AIE纳米材料中的AIE分子无需特性基团来修饰，这一方面降低了材料设计的繁琐性，另一方面提供了结合其他功能(例如光动力治疗、光声成像和光热治疗等)的可能性"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "51",
"type": "bibr",
"rid": "R51",
"data": [
{
"name": "text",
"data": "51"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "53",
"type": "bibr",
"rid": "R53",
"data": [
{
"name": "text",
"data": "53"
}
]
}
}
],
"rid": [
"R51",
"R52",
"R53"
],
"text": "51-53",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。Tian等"
},
{
"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": "开发了一种基于DNA四面体结构的纳米荧光探针。其四面体的顶角分别修饰了TPP、对pH响应的荧光素和对钙离子响应的碳点等功能组件。其中，TPP可以诱使纳米探针靶向细胞线粒体，同时在超氧自由基和聚集"
},
{
"name": "italic",
"data": [
{
"name": "text",
"data": "β"
}
]
},
{
"name": "text",
"data": "淀粉样蛋白的刺激下使探针实现对pH和钙离子的荧光检测。这预示了通过在AIE纳米材料表面直接修饰TPP等线粒体靶向基团，可便捷地得到靶向细胞线粒体的AIE纳米荧光探针("
},
{
"name": "xref",
"data": {
"text": "图4",
"type": "fig",
"rid": "F4",
"data": [
{
"name": "text",
"data": "图4"
}
]
}
},
{
"name": "text",
"data": ")。"
}
]
},
{
"name": "fig",
"data": {
"id": "F4",
"caption": [
{
"lang": "zh",
"label": [
{
"name": "text",
"data": "图4"
}
],
"title": [
{
"name": "text",
"data": "线粒体靶向AIE纳米探针设计示意图"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "51",
"type": "bibr",
"rid": "R51",
"data": [
{
"name": "text",
"data": "51"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
}
]
},
{
"lang": "en",
"label": [
{
"name": "text",
"data": "Fig.4"
}
],
"title": [
{
"name": "text",
"data": "Schematic diagram of designing AIE nanoprobe for mitochondria targeting and imaging"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "51",
"type": "bibr",
"rid": "R51",
"data": [
{
"name": "text",
"data": "51"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
}
]
}
],
"subcaption": [],
"note": [],
"graphics": [
{
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},
{
"name": "sec",
"data": [
{
"name": "sectitle",
"data": {
"title": [
{
"name": "text",
"data": "3 线粒体靶向AIE探针的癌细胞识别"
}
],
"level": "1",
"id": "s3"
}
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "线粒体是真核生物细胞的能量工厂。据研究，肿瘤细胞中线粒体的代谢活性与正常细胞有明显区别，因此可作为利用线粒体荧光探针来识别癌细胞的主要依据"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "55",
"type": "bibr",
"rid": "R55",
"data": [
{
"name": "text",
"data": "55"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "56",
"type": "bibr",
"rid": "R56",
"data": [
{
"name": "text",
"data": "56"
}
]
}
}
],
"rid": [
"R55",
"R56"
],
"text": "55-56",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。目前线粒体AIE探针在癌细胞识别方面的主要应用有癌细胞与正常细胞区别成像、循环肿瘤细胞与白细胞区别成像以及癌细胞与相关细菌双重靶向成像。"
}
]
},
{
"name": "sec",
"data": [
{
"name": "sectitle",
"data": {
"title": [
{
"name": "text",
"data": "3.1 癌细胞与正常细胞区别成像"
}
],
"level": "2",
"id": "s3a"
}
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "Tang等"
},
{
"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": "以HeLa细胞作为模型研究发现TPE-IQ-2O能对其线粒体进行很好的染色，并且其成像信号可以和商业化染料Mito Tracker Red有很好的重叠，表明这种AIE染料具有极佳的成像选择性。相反，这种AIE染料在相同条件下并不能富集在正常的COS-7细胞的线粒体内，因此不呈现成像信号。这表明基于线粒体成像的AIE荧光探针具有区分正常细胞与癌细胞的巨大潜力。进一步研究发现，TPE-IQ-2O同样可对MCF-7、PC-9、MDA-MB-231和A549等其他癌细胞的线粒体进行靶向成像，而对于HEK-293和MDCK-Ⅱ正常细胞却没有染色效果。此外，在正常细胞和癌细胞共培养的体系中，TPE-IQ-2O只能选择性地点亮癌细胞("
},
{
"name": "xref",
"data": {
"text": "图5",
"type": "fig",
"rid": "F5",
"data": [
{
"name": "text",
"data": "图5"
}
]
}
},
{
"name": "text",
"data": ")。因此。TPE-IQ-2O是一种基于线粒体成像并且可广泛区分癌细胞和正常细胞的荧光探针，从而在成像介导的肿瘤手术中(可用于判断肿瘤残余是否完全清除)具有极大用途。"
}
]
},
{
"name": "fig",
"data": {
"id": "F5",
"caption": [
{
"lang": "zh",
"label": [
{
"name": "text",
"data": "图5"
}
],
"title": [
{
"name": "text",
"data": "(a)～(h)TPE-IQ-2O对常见癌细胞和正常细胞的线粒体成像，HeLa细胞和COS-7细胞成像图片中标尺相同，其余细胞成像标尺相同；(i)TPE-IQ-2O对不同种类细胞线粒体成像的相对荧光强度；(j)～(m)TPE-IQ-2O用于癌细胞和正常细胞的区分成像"
},
{
"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": "。"
}
]
},
{
"lang": "en",
"label": [
{
"name": "text",
"data": "Fig.5"
}
],
"title": [
{
"name": "text",
"data": "(a)－(h)Mitochondria imaging of common cancer cells and normal cells with TPE-IQ-2O. The bar is same for HeLa and COS-7 images while the others have the same bar. (i)Relative fluorescent intensity of TPE-IQ-2O in cell imaging. (j)－(m)Distinguishing imaging of TPE-IQ-2O between cancer cells and normal cells"
},
{
"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": "．"
}
]
}
],
"subcaption": [],
"note": [],
"graphics": [
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{
"name": "p",
"data": [
{
"name": "text",
"data": "Tang等"
},
{
"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": "合成了十二碳烷基链修饰的吡啶盐类线粒体探针IVPI-12。IVPI-12中的长烷基链可以和线粒体膜的脂质双分子层产生强的疏水相互作用，因此可以在不考虑线粒体膜电位变化的前提下，长期靶向线粒体。尽管如此，IVPI-12中的碘离子由于其重原子效应会导致荧光猝灭，从而降低探针的成像效果。为此，Tang等"
},
{
"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": "通过缩短烷基链长度和用六氟磷酸根离子置换碘离子制备了AIE分子IVP-02("
},
{
"name": "xref",
"data": {
"text": "图6(a)",
"type": "fig",
"rid": "F6",
"data": [
{
"name": "text",
"data": "图6(a)"
}
]
}
},
{
"name": "text",
"data": ")。IVP-02对癌细胞和正常细胞有非常好的区分能力：通过将不同癌细胞和不同正常细胞共培养并用IVP-02染色发现只有癌细胞(A549和HeLa细胞)中的线粒体被点亮，而正常细胞(COS-7和HLF细胞)几乎没有荧光信号("
},
{
"name": "xref",
"data": {
"text": "图6(b)",
"type": "fig",
"rid": "F6",
"data": [
{
"name": "text",
"data": "图6(b)"
}
]
}
},
{
"name": "text",
"data": ")。为了更为精准地探查IVP-02对癌细胞的选择性，作者分别将带有癌细胞(A549细胞)和正常细胞(HLF细胞)的盖玻片放于同一培养皿中，并同时使用IVP-02染色，结果显示只有带有癌细胞的玻璃片上的细胞才能被点亮，而带有正常细胞的玻璃片仍无荧光信号("
},
{
"name": "xref",
"data": {
"text": "图6(c)",
"type": "fig",
"rid": "F6",
"data": [
{
"name": "text",
"data": "图6(c)"
}
]
}
},
{
"name": "text",
"data": ")。以上结果表明IVP-02可以选择性标记癌细胞的线粒体，从而实现癌细胞与正常细胞的区分。"
}
]
},
{
"name": "fig",
"data": {
"id": "F6",
"caption": [
{
"lang": "zh",
"label": [
{
"name": "text",
"data": "图6"
}
],
"title": [
{
"name": "text",
"data": "(a)IVP-02及其衍生物的分子结构；(b)～(c)IVP-02用于区分癌细胞与正常细胞的成像。图中标尺为50 μm"
},
{
"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": "。"
}
]
},
{
"lang": "en",
"label": [
{
"name": "text",
"data": "Fig.6"
}
],
"title": [
{
"name": "text",
"data": "(a)Molecular structures of IVP-02 and its derivatives. (b)－(c)Distinguishing imaging of IVP-02 between cancer cells and normal cells, the bar is 50 μm"
},
{
"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": "．"
}
]
}
],
"subcaption": [],
"note": [],
"graphics": [
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},
{
"name": "p",
"data": [
{
"name": "text",
"data": "Tang等还发现TPE-2EP@CB[8]、TPE-3EP@CB[8]"
},
{
"name": "text",
"data": "和TPE-4EP@CB[8]组装体的大小和形状对线粒体成像的效果有明显的影响("
},
{
"name": "xref",
"data": {
"text": "图7(a)",
"type": "fig",
"rid": "F7",
"data": [
{
"name": "text",
"data": "图7(a)"
}
]
}
},
{
"name": "text",
"data": ")"
},
{
"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": "。其中，TPE-2EP@CB[8]组装体的尺寸最小(200～250 nm)，易于和T24癌细胞作用，具有最佳的成像效果。TPE-3EP@CB[8]"
},
{
"name": "text",
"data": "和TPE-4EP@CB[8]组装体的尺寸相接近(400～500 nm)，但二者的形状分别为球形和立方形。由于球形纳米体相比于立方形纳米体更易于进入细胞，因此TPE-3EP@CB[8]"
},
{
"name": "text",
"data": "具有较好的成像效果。此外，对于同一种组装体，它们对于不同细胞系(包括SV-HUC-1正常细胞、T24和UMUC3癌细胞、DU145和HeLa转移癌细胞)具有不同的成像效果。这种成像强度的差别不仅体现在单独的不同的细胞系上，还体现在不同比例的混合细胞系上，因此可作为辨别它们的“指纹”信号。利用3种组装体的成像信号，结合线性判别分析，作者绘制了分类模式图("
},
{
"name": "xref",
"data": {
"text": "图7(b)～(d)",
"type": "fig",
"rid": "F7",
"data": [
{
"name": "text",
"data": "图7(b)～(d)"
}
]
}
},
{
"name": "text",
"data": ")。这种模式图不仅可以对不同的正常细胞、癌细胞和转移癌细胞进行分类，还可以半定量鉴别不同癌细胞混合体系以及正常细胞和癌细胞混合体系中各组分的含量(在图中显示为各自信号区域独立且不重叠)。因此，该项工作对临床癌症诊断、术后肿瘤清除程度的评价和细胞系种类及污染程度的鉴定等方面具有极大的帮助。"
}
]
},
{
"name": "fig",
"data": {
"id": "F7",
"caption": [
{
"lang": "zh",
"label": [
{
"name": "text",
"data": "图 7"
}
],
"title": [
{
"name": "text",
"data": "(a)TPE-2EP@CB[8]、TPE-3EP@CB[8]"
},
{
"name": "text",
"data": "和TPE-4EP@CB[8]主客体复合物的线粒体成像，图中标尺为10 μm；基于成像强度和大数据分析鉴别不同的癌细胞(b)、混合癌细胞中各组分(c)以及混合的正常细胞和癌细胞各组分(d)"
},
{
"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": "。"
}
]
},
{
"lang": "en",
"label": [
{
"name": "text",
"data": "Fig.7"
}
],
"title": [
{
"name": "text",
"data": "(a)Mitochondria imaging with TPE-2EP@CB[8], TPE-3EP@CB[8]"
},
{
"name": "text",
"data": "和TPE-4EP@CB[8] host-guest complexes. Identification of different cancer cells(b), composition of cancer cell mixture(c) and cancer and normal cell mixture(d) based on imaging intensity and big data anlysis"
},
{
"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": "．"
}
]
}
],
"subcaption": [],
"note": [],
"graphics": [
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},
{
"name": "sec",
"data": [
{
"name": "sectitle",
"data": {
"title": [
{
"name": "text",
"data": "3.2 循环肿瘤细胞与白细胞区别成像"
}
],
"level": "2",
"id": "s3b"
}
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "循环肿瘤细胞存在于癌症患者的血液中，被认为是肿瘤转移的“种子”，循环肿瘤细胞的定量分析将有利于癌症治疗的反应评估和后续复发监测"
},
{
"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": "。而白细胞是血液中最丰富的真核细胞，因此区分白细胞和循环肿瘤细胞在医学诊断领域具有实际意义。而正常细胞和癌细胞中线粒体由于膜电位存在差异，能对带正电荷的线粒体探针产生不同的亲和性，因此可设计靶向线粒体的荧光探针用于区分白细胞和循环肿瘤细胞。Zheng等"
},
{
"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": "61",
"type": "bibr",
"rid": "R61",
"data": [
{
"name": "text",
"data": "61"
}
]
}
}
],
"rid": [
"R60",
"R61"
],
"text": "60-61",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "通过用一种由TPE和吡啶叠氮盐组成的具有AIE活性的线粒体荧光探针TPE-PyN"
},
{
"name": "sub",
"data": [
{
"name": "text",
"data": "3"
}
]
},
{
"name": "text",
"data": "("
},
{
"name": "xref",
"data": {
"text": "图8(a)",
"type": "fig",
"rid": "F8",
"data": [
{
"name": "text",
"data": "图8(a)"
}
]
}
},
{
"name": "text",
"data": ")，实现了在生命系统中的循环肿瘤细胞识别和无创成像，在肿瘤学、发育生物学和药物学等研究领域具有潜在应用前景。作者采用TPE-PyN"
},
{
"name": "sub",
"data": [
{
"name": "text",
"data": "3"
}
]
},
{
"name": "text",
"data": "在相同条件下分别对从血液中分离出的白细胞和7种不同的癌细胞(包括H1975、A549、SMMC-7721、HepG2、HT-29、MCF-7和HeLa细胞)染色后发现，仅白细胞显示出微弱的荧光信号，而7种癌细胞均发射明亮的黄色荧光("
},
{
"name": "xref",
"data": {
"text": "图8(b)",
"type": "fig",
"rid": "F8",
"data": [
{
"name": "text",
"data": "图8(b)"
}
]
}
},
{
"name": "text",
"data": ")"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "61",
"type": "bibr",
"rid": "R61",
"data": [
{
"name": "text",
"data": "61"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。这种荧光差异表明TPE-PyN"
},
{
"name": "sub",
"data": [
{
"name": "text",
"data": "3"
}
]
},
{
"name": "text",
"data": "具有在白细胞中区分癌细胞的潜力。作者随后在白细胞中掺入少量癌细胞来模拟真实样品环境。作者将已知数目的H1975癌细胞预先使用绿色荧光染料5-氯甲基二乙酸荧光素(CMFDA)标记，随后加入到白细胞中使用TPE-PyN"
},
{
"name": "sub",
"data": [
{
"name": "text",
"data": "3"
}
]
},
{
"name": "text",
"data": "和反CD45抗体(一种白细胞的检测物)进行共染色标记。实验发现，CMFDA和TPE-PyN"
},
{
"name": "sub",
"data": [
{
"name": "text",
"data": "3"
}
]
},
{
"name": "text",
"data": "的绿色荧光和黄色荧光信号可在H1975细胞中同时被发现。而白细胞主要发射CD45的红色荧光(有少量白细胞发射比较弱的TPE-PyN"
},
{
"name": "sub",
"data": [
{
"name": "text",
"data": "3"
}
]
},
{
"name": "text",
"data": "的黄色荧光)。这说明TPE-PyN"
},
{
"name": "sub",
"data": [
{
"name": "text",
"data": "3"
}
]
},
{
"name": "text",
"data": "能够较好地识别和区分真实环境中的癌细胞("
},
{
"name": "xref",
"data": {
"text": "图8(c)",
"type": "fig",
"rid": "F8",
"data": [
{
"name": "text",
"data": "图8(c)"
}
]
}
},
{
"name": "text",
"data": ")。相较于常规循环肿瘤细胞鉴定方法，使用TPE-PyN"
},
{
"name": "sub",
"data": [
{
"name": "text",
"data": "3"
}
]
},
{
"name": "text",
"data": "进行活细胞标记操作简单、成本低廉、对细胞生存力和完整性影响小，可以在单细胞水平上对癌细胞进行高质量分析，因此为鉴定不同类型的低含量循环肿瘤细胞提供了新的方法。"
}
]
},
{
"name": "fig",
"data": {
"id": "F8",
"caption": [
{
"lang": "zh",
"label": [
{
"name": "text",
"data": "图8"
}
],
"title": [
{
"name": "text",
"data": "(a)TPE-PyN"
},
{
"name": "sub",
"data": [
{
"name": "text",
"data": "3"
}
]
},
{
"name": "text",
"data": "的分子结构；(b)TPE-PyN"
},
{
"name": "sub",
"data": [
{
"name": "text",
"data": "3"
}
]
},
{
"name": "text",
"data": "对于白细胞和不同癌细胞的区分成像；(c)模拟真实样品环境中对于H1975癌细胞的识别。图中标尺为50 μm"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "61",
"type": "bibr",
"rid": "R61",
"data": [
{
"name": "text",
"data": "61"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。"
}
]
},
{
"lang": "en",
"label": [
{
"name": "text",
"data": "Fig.8"
}
],
"title": [
{
"name": "text",
"data": "(a)Molecular structure of TPE-PyN"
},
{
"name": "sub",
"data": [
{
"name": "text",
"data": "3"
}
]
},
{
"name": "text",
"data": ". (b)Distinguishing imaging of TPE-PyN"
},
{
"name": "sub",
"data": [
{
"name": "text",
"data": "3"
}
]
},
{
"name": "text",
"data": " between leukocyte and different cancer cells. (c)Identification of H1975 cancer cells from simulated real sample. The bar is 50 μm"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "61",
"type": "bibr",
"rid": "R61",
"data": [
{
"name": "text",
"data": "61"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "．"
}
]
}
],
"subcaption": [],
"note": [],
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"data": {
"title": [
{
"name": "text",
"data": "3.3 癌细胞和相关细菌与正常细胞的区分成像"
}
],
"level": "2",
"id": "s3c"
}
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "据研究，肿瘤微环境存在的细菌会通过代谢化疗药物和调节癌细胞自噬降低癌症的治疗效率"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "blockXref",
"data": {
"data": [
{
"name": "xref",
"data": {
"text": "62",
"type": "bibr",
"rid": "R62",
"data": [
{
"name": "text",
"data": "62"
}
]
}
},
{
"name": "text",
"data": "-"
},
{
"name": "xref",
"data": {
"text": "63",
"type": "bibr",
"rid": "R63",
"data": [
{
"name": "text",
"data": "63"
}
]
}
}
],
"rid": [
"R62",
"R63"
],
"text": "62-63",
"type": "bibr"
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。此外，某些革兰氏阳性菌(如梭形杆菌)会促进肿瘤生长和转移，而一些革兰氏阳性菌(如葡萄球菌和链球菌)则容易引起手术部位感染，从而影响术后的治愈"
},
{
"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": "。因此，能够同时检测和区分癌细胞和革兰氏阳性菌具有重要临床意义。Tang等"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "66",
"type": "bibr",
"rid": "R66",
"data": [
{
"name": "text",
"data": "66"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "设计合成了一种带吡啶盐的AIE分子TPPCN("
},
{
"name": "xref",
"data": {
"text": "图9(a)",
"type": "fig",
"rid": "F9",
"data": [
{
"name": "text",
"data": "图9(a)"
}
]
}
},
{
"name": "text",
"data": ")。作者首先将HeLa癌细胞和MDCK-Ⅱ正常细胞在同一培养皿中进行共培养，然后使用TPPCN染色，结果显示HeLa细胞的线粒体发射强的蓝绿色荧光，而在MDCK-Ⅱ细胞中几乎未检测到荧光信号。这证明了TPPCN可实现癌细胞与正常细胞的区分。由于革兰氏阳性菌相较于革兰氏阴性菌具有更简单的薄膜结构且异物屏障效果较弱，TPPCN将更倾向于进入革兰氏阳性菌，从而实现两类细菌的区分。作者将TPPCN和革兰氏阳性表皮葡萄球菌与革兰氏阴性大肠杆菌共同培育，结果显示前者被染色并发射蓝绿色荧光，而后者几乎未观察到荧光信号，因此TPPCN同时具有区分革兰氏阳性细菌和革兰氏阴性细菌的能力。最后，作者进一步研究了TTPCN同时成像癌细胞和革兰氏阳性细菌的能力。作者将HeLa细胞、MDCK-Ⅱ正常细胞和革兰氏阳性表皮葡萄球菌在同一培养皿中共培养并用TPPCN染色，结果显示在HeLa细胞和革兰氏阳性表皮葡萄球菌中均可以检测到蓝绿色荧光，而在MDCK-Ⅱ正常细胞中仍检测不到荧光信号("
},
{
"name": "xref",
"data": {
"text": "图9(b)～(d)",
"type": "fig",
"rid": "F9",
"data": [
{
"name": "text",
"data": "图9(b)～(d)"
}
]
}
},
{
"name": "text",
"data": ")，证明TPPCN确实可以同时实现对癌细胞和革兰氏阳性细菌的双重靶向成像。该项研究不仅验证了AIE分子区分癌细胞和正常细胞的能力，同时将其扩展到了革兰氏阳性细菌的标记，可促进对癌症诊断和治疗中癌细胞和相关细菌的检测。"
}
]
},
{
"name": "fig",
"data": {
"id": "F9",
"caption": [
{
"lang": "zh",
"label": [
{
"name": "text",
"data": "图9"
}
],
"title": [
{
"name": "text",
"data": "(a)TPPCN的分子结构；(b)～(d)TPPCN用于同时区分HeLa细胞和革兰氏阳性表皮葡萄球菌"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "66",
"type": "bibr",
"rid": "R66",
"data": [
{
"name": "text",
"data": "66"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。"
}
]
},
{
"lang": "en",
"label": [
{
"name": "text",
"data": "Fig.9"
}
],
"title": [
{
"name": "text",
"data": "(a)Molecular structure of TPPCN. (b)－(d)Simultaneous distinguishing of HeLa cell and S. epidermidis with TPPCN"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "66",
"type": "bibr",
"rid": "R66",
"data": [
{
"name": "text",
"data": "66"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "．"
}
]
}
],
"subcaption": [],
"note": [],
"graphics": [
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{
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"data": [
{
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"data": {
"title": [
{
"name": "text",
"data": "4 靶向癌细胞线粒体机理研究"
}
],
"level": "1",
"id": "s4"
}
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "AIE荧光探针特异性标记癌细胞线粒体的机理研究主要从线粒体膜电位差异和荧光探针本身的化学结构进行总结分析。"
}
]
},
{
"name": "sec",
"data": [
{
"name": "sectitle",
"data": {
"title": [
{
"name": "text",
"data": "4.1 线粒体膜电位影响"
}
],
"level": "2",
"id": "s4a"
}
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "与正常细胞相比，癌细胞具有更高的线粒体膜电位，当细胞代谢活跃时，线粒体膜电位至少相差60 mV"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "67",
"type": "bibr",
"rid": "R67",
"data": [
{
"name": "text",
"data": "67"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "。Tang等"
},
{
"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": "通过对照实验证明了癌细胞线粒体膜电位更高是AIE荧光探针主要富集在其中的主要原因之一。作者先用羰基氰化间氯苯基腙(CCCP)对HeLa细胞进行预处理使其线粒体膜电位降低，然后通过TPE-IQ-2O染色只观察到比较弱的荧光("
},
{
"name": "xref",
"data": {
"text": "图2",
"type": "fig",
"rid": "F2",
"data": [
{
"name": "text",
"data": "图2"
}
]
}
},
{
"name": "text",
"data": ")。此外，对HeLa细胞先染色后再用CCCP处理也会出现荧光减弱的现象。相反，当使用寡霉素对HeLa细胞预处理使其膜电位升高时，细胞可以呈现较强的荧光发射。另外，死亡的HeLa细胞由于不存在膜电位几乎不发射荧光。这一系列现象表明线粒体膜电位的高低将显著影响AIE荧光探针与HeLa细胞之间的静电相互作用，进而用于对癌细胞和正常细胞的区分("
},
{
"name": "xref",
"data": {
"text": "图10",
"type": "fig",
"rid": "F10",
"data": [
{
"name": "text",
"data": "图10"
}
]
}
},
{
"name": "text",
"data": ")。同时，癌细胞和正常细胞这种膜电位的差别也证实了对于带正电荷的AIE探针的需求。作者研究了5种带正电荷的具有不同化学结构的AIE探针，发现探针对癌细胞和正常细胞的区分主要和其上的正电荷基团相关，而受探针其他部位化学结构影响较小。"
}
]
},
{
"name": "fig",
"data": {
"id": "F10",
"caption": [
{
"lang": "zh",
"label": [
{
"name": "text",
"data": "图10"
}
],
"title": [
{
"name": "text",
"data": "癌症细胞和正常细胞线粒体膜电位差异示意图"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "34",
"type": "bibr",
"rid": "R34",
"data": [
{
"name": "text",
"data": "34"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
}
]
},
{
"lang": "en",
"label": [
{
"name": "text",
"data": "Fig.10"
}
],
"title": [
{
"name": "text",
"data": "Schematic illustration of the difference of membrane potential between cancer cells and normal cells"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "34",
"type": "bibr",
"rid": "R34",
"data": [
{
"name": "text",
"data": "34"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
}
]
}
],
"subcaption": [],
"note": [],
"graphics": [
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"data": [
{
"name": "sectitle",
"data": {
"title": [
{
"name": "text",
"data": "4.2 荧光探针本身化学结构的影响"
}
],
"level": "2",
"id": "s4b"
}
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "据报道，某些对线粒体膜电位很敏感的商业线粒体探针可同时染色癌细胞和正常细胞"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "68",
"type": "bibr",
"rid": "R68",
"data": [
{
"name": "text",
"data": "68"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
},
{
"name": "text",
"data": "，因此膜电位不是荧光探针区分癌细胞和正常细胞的唯一原因，探针的膜通透性也是其区别成像的重要因素之一。Tang等"
},
{
"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": "基于IVP-02在吡啶盐或吲哚一侧延长烷基链得到了IVP-04、IVP-06、IVP-22、IVP-42和IVP-62五种AIE衍生物("
},
{
"name": "xref",
"data": {
"text": "图6(a)",
"type": "fig",
"rid": "F6",
"data": [
{
"name": "text",
"data": "图6(a)"
}
]
}
},
{
"name": "text",
"data": ")。分子中烷基链的位置及长度将会影响其与线粒体脂质双分子层的相互作用，从而调节对膜的通透性。"
}
]
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "作者通过使用这6种荧光探针对共培养的COS-7正常细胞和A549癌细胞染色，发现只有IVP-02、IVP-22、IVP-42和IVP-62能使A549癌细胞发射成像信号，说明它们可以明显区分癌细胞和正常细胞，而IVP-04和IVP-06却能同时染色A549癌细胞和COS-7正常细胞，因此无法实现癌细胞筛选标记。基于这些成像结果，作者得出IVP分子对癌细胞的选择性主要由吡啶盐侧烷基链的长度决定，且延长该位点烷基链的长度将会消除探针对癌细胞的特异性选择。"
}
]
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "由于这些IVP分子中均含有带吡啶盐的正电荷基团，该侧更为亲水，因此将会富集更多的水分子，从而决定离子半径。IVP-04和IPV-06相比于其余分子，拥有更长的吡啶盐侧烷基链，使得它们的离子半径增大，从而减弱与水分子之间的相互作用(即增强了与脂质双分子层疏水相互作用)，因此它们能无选择性地同时染色正常细胞和癌细胞("
},
{
"name": "xref",
"data": {
"text": "图11",
"type": "fig",
"rid": "F11",
"data": [
{
"name": "text",
"data": "图11"
}
]
}
},
{
"name": "text",
"data": ")。"
}
]
},
{
"name": "fig",
"data": {
"id": "F11",
"caption": [
{
"lang": "zh",
"label": [
{
"name": "text",
"data": "图11"
}
],
"title": [
{
"name": "text",
"data": "亲脂性阳离子通过膜示意图"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "58",
"type": "bibr",
"rid": "R58",
"data": [
{
"name": "text",
"data": "58"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
}
]
},
{
"lang": "en",
"label": [
{
"name": "text",
"data": "Fig.11"
}
],
"title": [
{
"name": "text",
"data": "Schematic diagram of lipophilic cation passing through the membrane"
},
{
"name": "sup",
"data": [
{
"name": "text",
"data": "["
},
{
"name": "xref",
"data": {
"text": "58",
"type": "bibr",
"rid": "R58",
"data": [
{
"name": "text",
"data": "58"
}
]
}
},
{
"name": "text",
"data": "]"
}
]
}
]
}
],
"subcaption": [],
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"title": [
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"name": "text",
"data": "5 结论与展望"
}
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{
"name": "p",
"data": [
{
"name": "text",
"data": "荧光成像技术是癌症诊断的重要手段之一。AIE探针由于其独特的光物理性质，可提高其成像的灵敏度和光稳定性，因此有望用于长期示踪生物分析识别和成像。根据线粒体膜电位在癌细胞和正常细胞中的差异，设计带三苯基膦盐、吡啶及吡啶衍生物盐和花菁盐等正电荷基团的AIE分子有利于增加探针和癌细胞线粒体膜的静电相互作用，提高对癌细胞的识别效果。此外，通过主客体相互作用和纳米粒子外修饰法也可得到用于对癌细胞区别成像的AIE纳米荧光探针。这些荧光探针可实现对癌细胞与正常细胞、循环肿瘤细胞与白细胞以及癌细胞和相关细菌与正常细胞的区别成像，因此在癌症诊断、手术导航、癌症治疗的反应评估及后续复发监测和细胞污染评估等方面具有广阔的应用前景。此外，除了膜电位的影响外，AIE探针本身的结构对区分癌细胞与正常细胞也有明显影响：当盐类基团外延的烷基链延长时，将会增大探针的离子半径，增加探针与脂质双分子层的疏水相互作用，从而不利于针对膜电位差异区分癌细胞与正常细胞。"
}
]
},
{
"name": "p",
"data": [
{
"name": "text",
"data": "虽然线粒体靶向AIE探针在识别癌细胞方面的研究取得了长足进步，但仍有许多发展空间，其未来的发展属于挑战与机遇并存。例如，进一步提高荧光探针的灵敏度有利于增强对微量癌细胞/微小肿瘤的识别；提高荧光探针的药物活性可以达到诊断与治疗的双重效果；而开发具有近红外吸收/发射的荧光探针，并结合双光子/三光子激发技术，将会大大提高荧光探针的成像深度，促进成像应用。我们坚信，通过国内外众多科学家的不懈坚持和努力，这类AIE荧光探针必将得到进一步优化升级，最终满足临床诊断成像，造福人类。"
}
]
}
]
}
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"response": [],
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"conflict": [],
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"articlemeta": {
"doi": "10.37188/CJL.20200351",
"clc": [
[
{
"name": "text",
"data": "O482.31"
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"dc": [
{
"name": "text",
"data": "A"
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"publisherid": "1000-7032(2021)03-0348-13",
"citeme": [],
"fundinggroup": [
{
"lang": "zh",
"text": [
{
"name": "text",
"data": "国家自然科学基金（21905113，21788102，51620105009）;广东省自然科学基金（2020A1515010622，2019B030301003，2016A030312002）;香港创新及科技基金（ITC-CNERC14S01）;中央高校基本科研业务费专项资金（21619316）资助项目"
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},
{
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"text": [
{
"name": "text",
"data": "Supported by National Natural Science Foundation of China (21905113, 21788102, 51620105009); Natural Science Foundation of Guangdong Province (2020A1515010622, 2019B030301003, 2016A030312002); Innovation and Technology Commission of Hong Kong (ITC-CNERC14S01); Fundamental Research Funds for the Central Universities (21619316)"
}
]
}
],
"history": {
"received": "2020-11-15",
"revised": "2020-12-05",
"ppub": "2021-03-01",
"opub": "2021-10-22"
},
"copyright": {
"data": [],
"year": "2021"
}
},
"appendix": [],
"type": "research-article",
"ethics": [],
"supplementary": [],
"journalTitle": "发光学报",
"issue": "03",
"volume": "42",
"originalSource": []
}
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