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用于高表达PD-L1肿瘤靶向诊疗的多价适配体功能化近红外二区量子点

Polyvalent Aptamer-Functionalized NIR-II Quantum Dots for Targeted Theranostics in High PD-L1-Expressing Tumors.

作者信息

Huang Xin, Zhu Jiawei, Dong Chuhuang, Li Yuqing, Yu Qing, Wang Xuan, Chen Zhejie, Li Jiabei, Yang Yu, Wang Haifang

机构信息

Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444, China.

Institute of Molecular Medicine (IMM), Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, P. R. China.

出版信息

ACS Appl Mater Interfaces. 2024 May 1;16(17):21571-21581. doi: 10.1021/acsami.4c01486. Epub 2024 Apr 18.

DOI:10.1021/acsami.4c01486
PMID:38636085
Abstract

AgS quantum dots (QDs) show superior optical properties in the NIR-II region and display significant clinical potential with favorable biocompatibility. However, inherent defects of low targeting and poor solubility necessitate practical modification methods to achieve the theranostics of AgS QDs. Herein, we used rolling circle amplification (RCA) techniques to obtain long single-stranded DNA containing the PD-L1 aptamer and C-rich DNA palindromic sequence. The C-rich DNA palindromic sequences can specifically chelate Ag and thus serve as a template to result in biomimetic mineralization and formation of pApt-AgS QDs. These QDs enable specific targeting and illuminate hot tumors with high PD-L1 expression effectively, serving as excellent molecular targeted probes. In addition, due to the high NIR-II absorption of AgS QDs, pApt-AgS QDs exhibit remarkable photothermal properties. And besides, polyvalent PD-L1 aptamers can recognize PD-L1 protein and effectively block the inhibitory signal of PD-L1 on T cells, enabling efficient theranostics through the synergistic effect of photothermal therapy and immune checkpoint blocking therapy. Summary, we enhance the biological stability and antibleaching ability of AgS QDs using long single-stranded DNA as a template, thereby establishing a theranostic platform that specifically targets PD-L1 high-expressing inflamed tumors and demonstrates excellent performance both and .

摘要

硫化银量子点(QDs)在近红外二区显示出优异的光学性质,并具有良好的生物相容性,展现出显著的临床潜力。然而,其固有的低靶向性和低溶解性缺陷需要切实可行的修饰方法来实现硫化银量子点的诊疗应用。在此,我们利用滚环扩增(RCA)技术获得了包含程序性死亡配体1(PD-L1)适配体和富含C的DNA回文序列的长单链DNA。富含C的DNA回文序列可以特异性螯合银,从而作为模板导致仿生矿化并形成pApt-AgS量子点。这些量子点能够实现特异性靶向并有效照亮高表达PD-L1的热点肿瘤,成为出色的分子靶向探针。此外,由于硫化银量子点在近红外二区具有高吸收性,pApt-AgS量子点表现出显著的光热性质。而且,多价PD-L1适配体能够识别PD-L1蛋白并有效阻断PD-L1对T细胞的抑制信号,通过光热疗法和免疫检查点阻断疗法的协同作用实现高效诊疗。总之,我们以长单链DNA为模板提高了硫化银量子点的生物稳定性和抗漂白能力,从而建立了一个特异性靶向PD-L1高表达炎症肿瘤的诊疗平台,并在……和……方面均表现出色。

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