題目：一種以巨噬細胞衍生的拟态纳米囊泡（MNV）为纳米载体，同时输送顺铂和ERCC2小干扰RNA（siRNA），以增强膀胱癌化疗的疗效 顺铂为基础的化疗在肌层浸润性膀胱癌（MIBC）的治疗中扮演着重要角色，然而，除了肿瘤外的毒性和耐药性常常导致癌症复发和最终治疗失败。核苷酸切除修复基因修复交叉补体啮齿动物修复缺陷基因2（ERCC2）在癌细胞中功能损失与顺铂敏感性相关，而其过表达导致顺铂耐药性。ERCC2小干扰RNA（siRNA）剥除结合顺铂治疗可能改善膀胱癌患者的治疗效果。本研究旨在开发巨噬细胞衍生的拟态纳米囊泡（MNV）作为纳米平台，同时输送顺铂和ERCC2 siRNA，以增强膀胱癌化疗的疗效。通过体外和体内评估制备的纳米药物（MNV-Co）的细胞摄取、基因下调、抑制肿瘤效果和生物安全性，用作MIBC的协同治疗策略。结果表明，MNV-Co对MIBC具有高疗效且肿瘤外毒性低。此外，通过下调ERCC2 mRNA和蛋白水平，MNV-Co可以改善化疗敏感性，促进癌细胞凋亡，并有效抑制肿瘤生长。本研究提出了一种可能的方法，使用生物拟态纳米系统同时输送顺铂和ERCC2 siRNA来治疗膀胱癌。 版权所有 © 2023 Wolters Kluwer Health, Inc. 保留所有权利。

Cisplatin-based chemotherapy plays a vital role in the management of muscle-invasive bladder cancer (MIBC); however, off-tumor toxicity and resistance often lead to cancer recurrence and eventual treatment failure. The loss of function of the nucleotide excision repair gene excision repair cross-complementing rodent repair deficiency gene 2 (ERCC2) in cancer cells correlates with sensitivity to cisplatin, while its overexpression causes cisplatin resistance. Small interfering RNA (siRNA) knockdown of ERCC2 combined with cisplatin treatment may improve therapeutic outcomes in patients with bladder cancer. Here, we aimed to develop macrophage-derived mimetic nanovesicles (MNVs) as a nanoplatform for the simultaneous delivery of cisplatin and ERCC2 siRNA for enhancing the efficacy of bladder cancer chemotherapy. The cellular uptake, gene down-regulation, tumor inhibition effects, and biosafety of the synthesized nanodrugs (MNV-Co) as a synergistic therapeutic strategy for MIBC were evaluated in vitro and in vivo. The results indicated high efficacy of MNV-Co against MIBC and low off-tumor toxicity. Furthermore, by down-regulating ERCC2 mRNA and protein levels, MNV-Co improved chemosensitivity, promoted cancer cell apoptosis, and effectively suppressed tumor growth. This study presents a potential approach for delivering cisplatin and ERCC2 siRNA concurrently to treat bladder cancer using a biomimetic nanosystem.Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.