这项研究探索了一种治疗腹膜转移 (PM) 的新方法，利用 AAV 介导的肿瘤抑制基因 microRNA-29b (miR-29b) 递送至腹膜间皮细胞 (PMC)。 AAV 血清型 2 和 DJ 分别对人和鼠 PMC 表现出高转导效率。体外分析表明，编码miR-29b前体的AAV载体成功提高PMC及其分泌的小细胞外囊泡（sEV）中miR-29b的表达，从而抑制间皮间质转化并减少随后的肿瘤细胞附着。 AAV-DJ-miR-29b 的单次腹膜内 (IP) 给药表现出强大且持续的转基因表达，抑制腹膜纤维化并抑制胃癌和胰腺癌 PM 的发展。此外，AAV-DJ-miR-29b 还可增强使用紫杉醇的腹膜内化疗的疗效，抑制已形成的 PM 的生长。虽然传统的癌症基因治疗面临直接靶向肿瘤细胞的挑战，但将 miRNA 递送至肿瘤基质提供了一种改变微环境的直接有效的方法，从而显着抑制肿瘤生长。 AAV 介导的 miR-29b 通过 IP 途径递送至腹膜，为难治性 PM 提供了一种简单、微创且有前景的治疗策略。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

This study explores a novel therapeutic approach for peritoneal metastasis (PM) using AAV-mediated delivery of tumor suppressor microRNA-29b (miR-29b) to peritoneal mesothelial cells (PMC). AAV serotypes 2 and DJ demonstrate high transduction efficiency for human and murine PMC, respectively. In vitro analysis indicates that AAV vectors encoding miR-29b precursor successfully elevate miR-29b expression in PMC and their secreted small extracellular vesicle (sEV), thereby inhibiting mesothelial mesenchymal transition and reducing subsequent attachment of tumor cells. A single intraperitoneal (IP) administration of AAV-DJ-miR-29b demonstrates robust and sustained transgene expression, suppressing peritoneal fibrosis and inhibiting the development of PM from gastric and pancreatic cancers. Additionally, AAV-DJ-miR-29b enhances the efficacy of IP chemotherapy using paclitaxel, restraining the growth of established PM. While conventional gene therapy for cancer encounters challenges targeting tumor cells directly but delivering miRNA to the tumor stroma offers a straightforward and efficient means of altering the microenvironment, leading to substantial inhibition of tumor growth. AAV-mediated miR-29b delivery to peritoneum via IP route presents a simple, minimally invasive, and promising therapeutic strategy for refractory PM.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.