Tumor Cell Membrane Biomimetic Mesoporous Silicon Materials in Combination with PD-L1 Knockout Achieved through the CRISPR/Cas9 System for Targeted and Immunotherapeutic Purposes.

IF 4 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS
Bioconjugate Chemistry Pub Date : 2025-05-21 Epub Date: 2025-04-21 DOI:10.1021/acs.bioconjchem.5c00001
Jinjin Zhao, Xiaorou Wang, Haiguang Zhang, Qunmei Zhang, DeYing Bo, Hua Zhong, Luyang Jiao, Hongchang Yuan, Guangjian Lu
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引用次数: 0

Abstract

Nanoparticle-based drug delivery systems, which enable the effective and targeted delivery of chemotherapeutic drugs to tumors, have revolutionized cancer therapy. Mesoporous silicon materials (MSN) have emerged as promising candidates for drug delivery due to their unique properties. The therapeutic efficacy can be significantly enhanced when treatments exhibit both targeting and antiphagocytic properties. In this study, cell membranes extracted from B16-F10 cells were used to encapsulate carboplatin (CBP)-loaded MSN via physical extrusion. Additionally, we intratumorally injected a plasmid containing the CRISPR/Cas9 system to achieve PD-L1 knockout, thereby reactivating the immune system. The cell membrane coating endowed the CBP@MSN with excellent slow-release capability and cytocompatibility. Enhanced tumor cell uptake of CBP@MSN@M was observed due to homologous targeting by cancer cell membranes. Moreover, CBP@MSN@M demonstrated enhanced antitumor efficacy in vivo and promoted the proliferation of immune cells. Finally, the antitumor effect was further improved by the knockout of PD-L1 within the tumor microenvironment. These results suggest that the newly prepared CBP@MSN@M, combined with PD-L1 knockout, holds significant potential as an effective therapeutic approach for treating tumors.

肿瘤细胞膜仿生介孔硅材料结合PD-L1敲除通过CRISPR/Cas9系统实现靶向和免疫治疗目的。
基于纳米颗粒的药物输送系统,使化疗药物能够有效和有针对性地输送到肿瘤,已经彻底改变了癌症治疗。介孔硅材料(MSN)由于其独特的性能而成为药物输送的有希望的候选者。当治疗同时具有靶向性和抗吞噬性时,治疗效果可以显著提高。在本研究中,我们从B16-F10细胞中提取细胞膜,通过物理挤压的方式包封卡铂(CBP)负载的MSN。此外,我们在瘤内注射含有CRISPR/Cas9系统的质粒来实现PD-L1敲除,从而重新激活免疫系统。细胞膜包被赋予CBP@MSN良好的缓释能力和细胞相容性。由于肿瘤细胞膜的同源靶向,观察到肿瘤细胞对CBP@MSN@M的摄取增强。此外,CBP@MSN@M在体内表现出增强的抗肿瘤功效,并促进免疫细胞的增殖。最后,通过敲除肿瘤微环境中的PD-L1进一步提高抗肿瘤效果。这些结果表明,新制备的CBP@MSN@M结合PD-L1敲除,具有作为治疗肿瘤的有效治疗方法的巨大潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Bioconjugate Chemistry
Bioconjugate Chemistry 生物-化学综合
CiteScore
9.00
自引率
2.10%
发文量
236
审稿时长
1.4 months
期刊介绍: Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.
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