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具有聚集诱导发射的超分子组装体用于癌细胞的原位主动成像指导光动力治疗。

Supramolecular assemblies with aggregation-induced emission for in situ active imaging-guided photodynamic therapy of cancer cells.

机构信息

School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, 430081, China.

School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, 430081, China; The State Key Laboratory of Refractories and Metallurgy, Wuhan University of Science and Technology, Wuhan, 430081, China.

出版信息

Talanta. 2024 Dec 1;280:126722. doi: 10.1016/j.talanta.2024.126722. Epub 2024 Aug 22.

DOI:10.1016/j.talanta.2024.126722
PMID:39186860
Abstract

Photodynamic therapy (PDT) has attracted widespread attention as a novel non-invasive anticancer approach. However, the diminished photosensitivity and limited oxygen exposure caused by the aggregation of traditional photosensitizers greatly impair its overall therapeutic efficacy. Herein, a series of water-soluble aggregation-induced emission luminogens (AIEgens) with triphenylamine as skeleton were synthesized and exhibited bright Near-infrared (NIR) emission and strong reactive oxygen species (ROS) generation. Through host-guest complexation between the multicharged triphenylamine units on AIEgens and cucurbit[10]uril (CB[10]) host molecule, supramolecular nanoassemblies were constructed and exhibited negligible phototoxicity to normal cells due to their limited oxygen contact. In contrast, the efficient release of AIEgens from nanoassemblies through competitive binding of overexpressed peptides in cancer cells with CB[10], enabled the full exploitation of the photosensitivity of AIEgens to produce highly efficient ROS, achieving selective ablation of cancer cells. Moreover, due to the restriction of intramolecular motion (RIM) upon anchored on organelle membranes through electrostatic interactions, the cationic AIEgens with weak fluorescence in physiological environment exhibited intense fluorescence emission, thus realizing imaging-guided PDT. This work may open up an avenue for the development of simple and feasible smart responsive nanomaterials for cancer treatment using supramolecular host-guest complexation strategy.

摘要

光动力疗法(PDT)作为一种新型的非侵入性抗癌方法引起了广泛关注。然而,传统光敏剂的聚集导致其光敏性降低和氧气暴露有限,极大地损害了其整体治疗效果。在此,我们合成了一系列以三苯胺为骨架的水溶性聚集诱导发光(AIE)材料,具有明亮的近红外(NIR)发射和强的活性氧(ROS)生成能力。通过 AIE 材料上的多电荷三苯胺单元与葫芦[10]脲(CB[10])主体分子之间的主客体络合作用,构建了超分子纳米组装体,由于其与氧气的接触有限,对正常细胞几乎没有光毒性。相比之下,通过癌细胞中过表达的肽与 CB[10]的竞争结合,从纳米组装体中有效释放 AIE 材料,充分利用了 AIE 材料的光敏性,产生高效的 ROS,实现了对癌细胞的选择性杀伤。此外,由于通过静电相互作用锚定在细胞器膜上时受到分子内运动的限制(RIM),在生理环境中荧光较弱的阳离子 AIE 材料表现出强烈的荧光发射,从而实现了成像引导的 PDT。这项工作可能为使用超分子主客体络合策略开发用于癌症治疗的简单可行的智能响应纳米材料开辟了一条新途径。

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