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具有前景的聚乙二醇化阳离子树枝状聚合物作为递送 miRNA 的载体，用于对抗 HIV-1 感染的可能疗法。

Promising PEGylated cationic dendrimers for delivery of miRNAs as a possible therapy against HIV-1 infection.

机构信息

Laboratorio InmunoBiología Molecular, Hospital General Universitario Gregorio Marañón (HGUGM), Instituto Investigación Sanitaria Gregorio Marañón (IiSGM), Spanish HIV HGM BioBanco, Madrid, Spain.

Plataforma de Laboratorio (Inmunología), HGUGM, IiSGM, Spanish HIV HGM BioBank, Madrid, Spain.

出版信息

J Nanobiotechnology. 2021 May 28;19(1):158. doi: 10.1186/s12951-021-00899-0.

DOI:10.1186/s12951-021-00899-0
PMID:34049570
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8161934/
Abstract

BACKGROUND

The appearance of resistance against new treatments and the fact that HIV-1 can infect various cell types and develop reservoirs and sanctuaries makes it necessary to develop new therapeutic approaches to overcome those failures.

RESULTS

Studies of cytotoxicity, genotoxicity, complexes formation, stability, resistance, release and particle size distribution confirmed that G2-SN15-PEG, G3-SN31-PEG, G2-SN15-PEG-FITC and G3-SN31-PEG-FITC dendrimers can form complexes with miRNAs being biocompatible, stable and conferring protection to these nucleic acids. Confocal microscopy and flow cytometry showed effective delivery of these four dendrimers into the target cells, confirming their applicability as delivery systems. Dendriplexes formed with the dendrimers and miRNAs significantly inhibited HIV-1 infection in PBMCs.

CONCLUSIONS

These dendrimers are efficient delivery systems for miRNAs and they specifically and significantly improved the anti-R5-HIV-1 activity of these RNA molecules.

摘要

背景

新治疗方法出现耐药性，以及 HIV-1 能够感染各种细胞类型并形成储库和避难所，这使得有必要开发新的治疗方法来克服这些失败。

结果

细胞毒性、遗传毒性、复合物形成、稳定性、耐药性、释放和粒径分布的研究证实，G2-SN15-PEG、G3-SN31-PEG、G2-SN15-PEG-FITC 和 G3-SN31-PEG-FITC 树突聚合物可以与 miRNA 形成复合物，具有生物相容性、稳定性，并对这些核酸提供保护。共聚焦显微镜和流式细胞术显示，这四种树突聚合物可以有效地递送到靶细胞中，证实了它们作为递药系统的适用性。树突聚合物与 miRNA 形成的树突聚合物可显著抑制 PBMC 中的 HIV-1 感染。

结论

这些树突聚合物是 miRNA 的有效递药系统，它们特异性和显著提高了这些 RNA 分子抗 R5-HIV-1 的活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/5888d39e68b7/12951_2021_899_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/d85ce0f1ac18/12951_2021_899_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/047d685bbd26/12951_2021_899_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/d7fe182b73a9/12951_2021_899_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/c81fa34a14ab/12951_2021_899_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/68a313919c2b/12951_2021_899_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/baa6019d5dd5/12951_2021_899_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/ac5b8be3d180/12951_2021_899_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/5888d39e68b7/12951_2021_899_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/d85ce0f1ac18/12951_2021_899_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/047d685bbd26/12951_2021_899_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/d7fe182b73a9/12951_2021_899_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/c81fa34a14ab/12951_2021_899_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/68a313919c2b/12951_2021_899_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/baa6019d5dd5/12951_2021_899_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/ac5b8be3d180/12951_2021_899_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/84ea/8161934/5888d39e68b7/12951_2021_899_Fig8_HTML.jpg

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