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具有ROS响应性的多药前体药物胶束携带自杀基因,联合化疗和基因疗法用于前列腺癌治疗。

ROS-responsive polyprodrug micelles carrying suicide genes in combination with chemotherapy and gene therapy for prostate cancer treatment.

作者信息

Li Kai, Tian Sinan, Sun Ke, Su Qingguo, Mei Yanhui, Niu Wenjie

机构信息

Department of Urology, Binzhou Medical University Hospital Binzhou Shandong 256500 P. R. China

出版信息

RSC Adv. 2024 Feb 13;14(8):5577-5587. doi: 10.1039/d4ra00352g. eCollection 2024 Feb 7.

Abstract

Prostate cancer is the most common malignant tumor in the male reproductive system, and its incidence increases with age. Chemotherapy is one of the main strategies for treating prostate cancer, but it often comes with unavoidable side effects. Nanocarriers can improve drug utilization and targeting, and cationic carriers can also carry nucleic acids for gene therapy. In this study, we prepared a cationic micelle constructed from a polyprodrug that can deliver both chemotherapeutic drugs and nucleic acids simultaneously. The typical chemotherapeutic drug hydroxycamptothecin (HCPT) was linked by reactive oxygen species (ROS)-responsive coupling agents and forms amphiphilic block polymers with low molecular weight polyethyleneimine (PEI). The resulting cationic micelles can be triggered by high levels of ROS in tumor cells and collapse to release HCPT and suicide genes to kill tumor cells. At the same time, it reduces the killing of normal cells. In prostate cancer cells, it has been confirmed that the co-delivery carriers combined with chemotherapy and a suicide gene prodrug system have shown an ideal therapeutic effect on prostate cancer.

摘要

前列腺癌是男性生殖系统中最常见的恶性肿瘤,其发病率随年龄增长而增加。化疗是治疗前列腺癌的主要策略之一,但它常常伴随着不可避免的副作用。纳米载体可以提高药物利用率和靶向性,阳离子载体还可以携带核酸用于基因治疗。在本研究中,我们制备了一种由聚前药构建的阳离子胶束,它可以同时递送化疗药物和核酸。典型的化疗药物羟基喜树碱(HCPT)通过活性氧(ROS)响应性偶联剂连接,并与低分子量聚乙烯亚胺(PEI)形成两亲性嵌段聚合物。所得的阳离子胶束可被肿瘤细胞中的高水平ROS触发并解体,释放HCPT和自杀基因以杀死肿瘤细胞。同时,它减少了对正常细胞的杀伤。在前列腺癌细胞中,已证实联合化疗和自杀基因前药系统的共递送载体对前列腺癌显示出理想的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c517/10862661/890004a19e5a/d4ra00352g-f1.jpg

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