PAMAM/miR-144 nanocarrier system inhibits the migration of gastric cancer by targeting mTOR signal transduction pathway.

IF 5.4 2区医学 Q1 BIOPHYSICS

Colloids and Surfaces B: Biointerfaces Pub Date : 2025-01-03 DOI:10.1016/j.colsurfb.2024.114492

Yayun Qian, Dongxu Zhu, Qiong Xu, Yujie Wang, Xiwen Chen, Weiwei Hua, Juqun Xi, Feng Lu

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Abstract

Exogenous microRNA-144 (miR-144) is considered as a potential biological drug for gastric cancer because of its biological activity to inhibit the epithelial-mesenchymal transition (EMT). However, the specific molecular mechanisms have not been fully revealed. In addition, their vulnerability to degradation by RNA enzymes in the blood limits their bioavailability. In this paper, a polyamidoamine (PAMAM)-wrapped miR-144 (PAMAM/miR-144) is prepared as a nanocarrier system to protect miR-144 from nuclease degradation. The PAMAM/miR-144 nanocarrier system achieves the optimal antitumor activity against gastric cancer migration and reduce mTOR protein expression by transferring miR-144 into human gastric cancer HGC-27 cells. At the same time, the PAMAM/miR-144 nanocarrier system significantly decreases the EMT via targeting mTOR signal pathway in HGC-27 cells and noticeably inhibited the growth of subcutaneous gastric cancer xenografts in nude mice. PAMAM/miR-144 nanocarrier system has effectively improved the bioavailability of miR-144, thus providing a promising combination modality for anticancer therapy.

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PAMAM/miR-144纳米载体系统通过靶向mTOR信号转导通路抑制胃癌的迁移。

外源性microRNA-144 （miR-144）具有抑制上皮-间质转化（epithelial-mesenchymal transition， EMT）的生物活性，被认为是治疗胃癌的潜在生物药物。然而，具体的分子机制尚未完全揭示。此外，它们易被血液中的RNA酶降解，限制了它们的生物利用度。本文制备了聚酰胺胺（PAMAM）包裹的miR-144 （PAMAM/miR-144）作为纳米载体体系来保护miR-144免受核酸酶降解。PAMAM/miR-144纳米载体系统通过将miR-144转移到人胃癌HGC-27细胞中，实现对胃癌迁移的最佳抗肿瘤活性，并降低mTOR蛋白的表达。同时，PAMAM/miR-144纳米载体系统通过靶向mTOR信号通路，显著降低HGC-27细胞的EMT，显著抑制裸鼠皮下胃癌异种移植物的生长。PAMAM/miR-144纳米载体体系有效提高了miR-144的生物利用度，为抗癌治疗提供了一种很有前景的联合方式。

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

Colloids and Surfaces B: Biointerfaces 生物-材料科学：生物材料

CiteScore

11.10

自引率

3.40%

发文量

730

审稿时长

42 days

期刊介绍： Colloids and Surfaces B: Biointerfaces is an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin, having particular relevance to the medical, pharmaceutical, biotechnological, food and cosmetic fields. Submissions that: (1) deal solely with biological phenomena and do not describe the physico-chemical or colloid-chemical background and/or mechanism of the phenomena, and (2) deal solely with colloid/interfacial phenomena and do not have appropriate biological content or relevance, are outside the scope of the journal and will not be considered for publication. The journal publishes regular research papers, reviews, short communications and invited perspective articles, called BioInterface Perspectives. The BioInterface Perspective provide researchers the opportunity to review their own work, as well as provide insight into the work of others that inspired and influenced the author. Regular articles should have a maximum total length of 6,000 words. In addition, a (combined) maximum of 8 normal-sized figures and/or tables is allowed (so for instance 3 tables and 5 figures). For multiple-panel figures each set of two panels equates to one figure. Short communications should not exceed half of the above. It is required to give on the article cover page a short statistical summary of the article listing the total number of words and tables/figures.