NGR-modified nanovesicles target ALKBH5 to inhibit ovarian cancer growth and metastasis.

IF 13.3 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Theranostics Pub Date : 2025-06-09 eCollection Date: 2025-01-01 DOI:10.7150/thno.107766

Cheng Du, DaLu Wang, Boquan Zhang, Yasong Zhao, Zheng He

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引用次数: 0

Abstract

Background: Immunotherapy resistance in ovarian cancer (OC) poses a significant clinical hurdle. This study aims to investigate the potential of NGR-modified biomimetic nanovesicles (NGR-BNVs) for delivering ALKBH5 siRNA to reverse this resistance. Methods: In vitro and in vivo experiments were conducted to assess the efficiency of NGR-modified nanovesicles in delivering ALKBH5 siRNA. OC cell proliferation was evaluated, and apoptosis induction was measured. A mouse xenograft model was utilized to examine the effects on tumor volume and metastasis. Tumor immune microenvironment (TIME) analysis was performed to determine changes in immune cell proportions and immunomodulatory factors. Results: NGR-modified nanovesicles effectively delivered ALKBH5 siRNA, leading to a significant inhibition of OC cell proliferation and apoptosis induction. Treated groups in the mouse xenograft model exhibited reduced tumor volume and decreased metastatic signals. Analysis of the immune microenvironment revealed an increased proportion of CD8⁺ T cells, reduced Tregs and MDSCs, and notable changes in key immunomodulatory factors. Conclusion: This study highlights the potential of NGR-modified BNVs for overcoming immunotherapy resistance in OC by delivering ALKBH5 siRNA, resulting in modulation of the immune microenvironment and promising therapeutic outcomes.

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ngr修饰的纳米囊泡靶向ALKBH5抑制卵巢癌生长和转移。

背景：卵巢癌（OC）免疫治疗耐药是一个重要的临床障碍。本研究旨在研究ngr修饰的仿生纳米囊泡（NGR-BNVs）递送ALKBH5 siRNA以逆转这种耐药性的潜力。方法：通过体外和体内实验，评价ngr修饰的纳米囊泡传递ALKBH5 siRNA的效率。观察OC细胞增殖情况，观察细胞凋亡诱导情况。采用小鼠异种移植瘤模型，观察其对肿瘤体积和转移的影响。肿瘤免疫微环境（TIME）分析确定免疫细胞比例和免疫调节因子的变化。结果：ngr修饰的纳米囊泡可有效递送ALKBH5 siRNA，显著抑制OC细胞增殖和诱导凋亡。在小鼠异种移植模型中，治疗组表现出肿瘤体积减小和转移信号减少。免疫微环境分析显示CD8+ T细胞比例增加，Tregs和MDSCs减少，关键免疫调节因子发生显著变化。结论：本研究强调了nrr修饰的bnv通过传递ALKBH5 siRNA来克服OC免疫治疗耐药的潜力，从而调节免疫微环境，并取得了良好的治疗效果。

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

Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

25.40

自引率

1.60%

发文量

433

审稿时长

1 months

期刊介绍： Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.