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用包裹小干扰RNA（siRNA）的聚乙二醇化脂质体靶向人乳头瘤病毒（HPV）感染的宫颈癌细胞及siRNA与聚乙烯亚胺复合的作用

Targeting HPV-infected cervical cancer cells with PEGylated liposomes encapsulating siRNA and the role of siRNA complexation with polyethylenimine.

作者信息

Levine Rachel M, Dinh Christina V, Harris Michael A, Kokkoli Efrosini

机构信息

Dept. of Chemical Engineering and Materials Science University of Minnesota Minneapolis MN 55455.

出版信息

Bioeng Transl Med. 2016 Aug 8;1(2):168-180. doi: 10.1002/btm2.10022. eCollection 2016 Jun.

DOI:10.1002/btm2.10022
PMID:29313012
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5675078/
Abstract

The greatest obstacle to clinical application of cancer gene therapy is lack of effective delivery tools. Gene delivery vehicles must protect against degradation, avoid immunogenic effects and prevent off target delivery which can cause harmful side effects. PEGylated liposomes have greatly improved tumor localization of small molecule drugs and are a promising tool for nucleic acid delivery as the polyethylene glycol (PEG) coating protects against immune recognition and blood clearance. In this study, small interfering RNA (siRNA) was fully encapsulated within PEGylated liposomes by complexing the siRNA with a cationic polymer, polyethyleneimine (PEI), before encapsulation. Formation methods and material compositions were then investigated for their effects on encapsulation. This technology was translated for protective delivery of siRNA designed for human papillomavirus (HPV) viral gene silencing and cervical cancer treatment. PEGylated liposomes encapsulating siRNA were functionalized with the AG86 targeting peptide-amphiphile which binds to the αβ integrin, a cervical cancer biomarker. It was found that both targeting and polymer complexation before encapsulation were critical components to effective transfection.

摘要

癌症基因治疗临床应用的最大障碍是缺乏有效的递送工具。基因递送载体必须防止降解、避免免疫原性效应并防止可能导致有害副作用的脱靶递送。聚乙二醇化脂质体极大地改善了小分子药物的肿瘤定位，并且作为核酸递送的一种有前景的工具，因为聚乙二醇（PEG）涂层可防止免疫识别和血液清除。在本研究中，在包封之前，通过将小分子干扰RNA（siRNA）与阳离子聚合物聚乙烯亚胺（PEI）复合，将其完全包封在聚乙二醇化脂质体中。然后研究形成方法和材料组成对包封的影响。该技术被转化用于保护性递送设计用于人乳头瘤病毒（HPV）病毒基因沉默和宫颈癌治疗的siRNA。包封siRNA的聚乙二醇化脂质体用与宫颈癌生物标志物αβ整合素结合的AG86靶向肽两亲物进行功能化。发现靶向和包封前的聚合物复合都是有效转染的关键组成部分。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/2e7b571fd028/BTM2-1-168-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/72853fb22dcc/BTM2-1-168-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/c7595f67f30b/BTM2-1-168-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/ed244e5cb0d0/BTM2-1-168-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/de4de650acbd/BTM2-1-168-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/fb8634ce57ed/BTM2-1-168-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/2e7b571fd028/BTM2-1-168-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/72853fb22dcc/BTM2-1-168-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/9d3ca4987da5/BTM2-1-168-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/1b27aa8d273c/BTM2-1-168-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/14a6c04fc834/BTM2-1-168-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/14f239224a96/BTM2-1-168-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/c7595f67f30b/BTM2-1-168-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/ed244e5cb0d0/BTM2-1-168-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/de4de650acbd/BTM2-1-168-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/fb8634ce57ed/BTM2-1-168-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35e/5675078/2e7b571fd028/BTM2-1-168-g010.jpg

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