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纳米乳剂辅助 siRNA 递送来调节神经肿瘤微环境治疗胰腺癌。

Nanoemulsion-Assisted siRNA Delivery to Modulate the Nervous Tumor Microenvironment in the Treatment of Pancreatic Cancer.

机构信息

Center for Drug Delivery and Nanomedicine, Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA.

出版信息

ACS Appl Mater Interfaces. 2022 Mar 2;14(8):10015-10029. doi: 10.1021/acsami.1c21997. Epub 2022 Feb 21.

DOI:10.1021/acsami.1c21997
PMID:35188730
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9153289/
Abstract

Pancreatic cancer (PC) is a fatal human cancer, whose progression is highly dependent on the nervous tumor microenvironment. In the present study, cationic perfluorocarbon nanoemulsions were employed as an intraperitoneal delivery platform to facilitate the delivery and penetration of a therapeutic small interfering RNA (siRNA) to orthotopic pancreatic tumors. The nanoemulsion was used to silence the expression of the nerve growth factor (NGF) as a way of favorably modulating the tumor-neuronal interactions in pancreatic tumors. The nanoemulsions exhibited deep tumor penetration that was dependent on exocytosis and enhanced NGF gene silencing and when compared with control polycation/siRNA polyplexes, leading to the effective and safe suppression of tumor growth in orthotopic PC. Overall, emulsion-assisted delivery of NGF siRNA is a promising treatment approach for PC by targeting the interactions between the tumor cells and the nervous microenvironment.

摘要

胰腺癌(PC)是一种致命的人类癌症,其进展高度依赖于神经肿瘤微环境。在本研究中,阳离子全氟碳纳米乳液被用作腹腔内递药平台,以促进治疗性小干扰 RNA(siRNA)递送至原位胰腺肿瘤并渗透进入其中。该纳米乳液被用于沉默神经生长因子(NGF)的表达,从而有利于调节胰腺肿瘤中的肿瘤-神经元相互作用。与对照聚阳离子/siRNA 聚合物相比,纳米乳液表现出深度的肿瘤渗透,这依赖于胞吐作用,并增强了 NGF 基因沉默,从而有效且安全地抑制了原位 PC 的肿瘤生长。总的来说,通过靶向肿瘤细胞与神经微环境之间的相互作用,利用乳液辅助递送 NGF siRNA 是一种很有前途的 PC 治疗方法。

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