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适配体修饰的基于锆的卟啉纳米级金属有机框架用于肿瘤的主动靶向化学-光动力治疗

Aptamer modified Zr-based porphyrinic nanoscale metal-organic frameworks for active-targeted chemo-photodynamic therapy of tumors.

作者信息

Feng Haidi, Zhao Lu, Bai Zhiqiang, Xin Zhihui, Wang Chaoyu, Liu Lizhen, Song Jinping, Zhang Haifei, Bai Yunfeng, Feng Feng

机构信息

School of Chemistry and Chemical Engineering, Shanxi Provincial Key Laboratory of Chemical Biosensing, Shanxi Datong University Datong 037009 P. R. China

School of Chemistry and Material Science, Shanxi Normal University Linfen 041004 P. R. China.

出版信息

RSC Adv. 2023 Apr 11;13(16):11215-11224. doi: 10.1039/d3ra00753g. eCollection 2023 Apr 3.

Abstract

Active-targeted nanoplatforms could specifically target tumors compared to normal cells, making them a promising therapeutic agent. The aptamer is a kind of short DNA or RNA sequence that can specifically bind to target molecules, and could be widely used as the active targeting agents of nanoplatforms to achieve active-targeted therapy of tumors. Herein, an aptamer modified nanoplatform DOX@PCN@Apt-M was designed for active-targeted chemo-photodynamic therapy of tumors. Zr-based porphyrinic nanoscale metal organic framework PCN-224 was synthesized through a one-pot reaction, which could produce cytotoxic O for efficient treatment of tumor cells. To improve the therapeutic effect of the tumor, the anticancer drug doxorubicin (DOX) was loaded into PCN-224 to form DOX@PCN-224 for tumor combination therapy. Active-targeted combination therapy achieved by modifying the MUC1 aptamer (Apt-M) onto DOX@PCN-224 surface can not only further reduce the dosage of therapeutic agents, but also reduce their toxic and side effects on normal tissues. , experimental results indicated that DOX@PCN@Apt-M exhibited enhanced combined therapeutic effect and active targeting efficiency under 808 nm laser irradiation for MCF-7 tumor cells. Based on PCN-224 nanocarriers and aptamer MUC1, this work provides a novel strategy for precisely targeting MCF-7 tumor cells.

摘要

与正常细胞相比,主动靶向纳米平台能够特异性地靶向肿瘤,使其成为一种有前景的治疗剂。适配体是一种能够特异性结合靶分子的短DNA或RNA序列,可广泛用作纳米平台的主动靶向剂,以实现肿瘤的主动靶向治疗。在此,设计了一种适配体修饰的纳米平台DOX@PCN@Apt-M用于肿瘤的主动靶向化学-光动力治疗。通过一锅法反应合成了基于锆的卟啉纳米级金属有机框架PCN-224,其可产生细胞毒性单线态氧以有效治疗肿瘤细胞。为提高肿瘤治疗效果,将抗癌药物阿霉素(DOX)负载到PCN-224中形成DOX@PCN-224用于肿瘤联合治疗。通过将MUC1适配体(Apt-M)修饰到DOX@PCN-224表面实现的主动靶向联合治疗不仅可以进一步降低治疗剂的用量,还可以减少其对正常组织的毒副作用。实验结果表明,DOX@PCN@Apt-M在808 nm激光照射下对MCF-7肿瘤细胞表现出增强的联合治疗效果和主动靶向效率。基于PCN-224纳米载体和适配体MUC1,这项工作为精确靶向MCF-7肿瘤细胞提供了一种新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4c2/10087063/8ad70b71bcc1/d3ra00753g-s1.jpg

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