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基于肽的双重功能胶束的智能药物传递。

Intelligent Drug Delivery by Peptide-Based Dual-Function Micelles.

机构信息

School of Chemical Engineering and Technology, Tiangong University, Tianjin 300387, China.

School of Chemistry, Tiangong University, Tianjin 300387, China.

出版信息

Int J Mol Sci. 2022 Aug 26;23(17):9698. doi: 10.3390/ijms23179698.

DOI:10.3390/ijms23179698
PMID:36077102
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9456463/
Abstract

To endow the polymeric prodrug with smart properties through a safe and simple method, matrix metalloproteinase (MMPs) responsive peptide GPLGVRGDG was introduced into the block copolymer to prepare TPGS-GPLGVRGDG-DOX&DOX micelles, where TPGS is D-α-tocopheryl polyethylene glycol 3350 succinate. During the doxorubicin delivery, the cleavage of the peptide chain triggers de-PEGylation, and the remaining VRGDG sequence was retained on the surface of the micelles, which can act as a ligand to facilitate cell uptake. Moreover, the cytotoxicity of TPGS-GPLGVRGDG-DOX&DOX micelles against 4T1 cells was significantly improved, compared with TPGS-GPLGVRG-DOX&DOX micelles and TPGS-DOX&DOX micelles. During in vivo studies, TPGS-GPLGVRGDG-DOX&DOX micelles exhibited good anticancer efficacy with long circulation in the body and more efficient accumulation at the tumor site. Therefore, TPGS-GPLGVRGDG-DOX&DOX micelles have improved antitumor activity and reduced toxic side effects. This work opens new potential for exploring the strategy of drug delivery in clinical applications.

摘要

为了通过安全简单的方法赋予聚合物前药智能特性，将基质金属蛋白酶（MMPs）响应肽 GPLGVRGDG 引入嵌段共聚物中，制备 TPGS-GPLGVRGDG-DOX&DOX 胶束，其中 TPGS 是 D-α-生育酚聚乙二醇 3350 琥珀酸酯。在阿霉素递送过程中，肽链的裂解触发去 PEG 化，并且剩余的 VRGDG 序列保留在胶束表面上，其可以作为配体促进细胞摄取。此外，与 TPGS-GPLGVRG-DOX&DOX 胶束和 TPGS-DOX&DOX 胶束相比，TPGS-GPLGVRGDG-DOX&DOX 胶束对 4T1 细胞的细胞毒性明显提高。在体内研究中，TPGS-GPLGVRGDG-DOX&DOX 胶束表现出良好的抗癌疗效，在体内具有长循环和更有效的肿瘤部位积累。因此，TPGS-GPLGVRGDG-DOX&DOX 胶束提高了抗肿瘤活性并降低了毒副作用。这项工作为探索临床应用中药物传递策略开辟了新的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/0239cd80b944/ijms-23-09698-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/e43939a4465f/ijms-23-09698-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/9e0846d1d298/ijms-23-09698-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/471496580ec2/ijms-23-09698-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/0e1ea7dcebe3/ijms-23-09698-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/7a96fdc51829/ijms-23-09698-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/8edc0ffddd64/ijms-23-09698-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/2175c146e61c/ijms-23-09698-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/fca9891f4c83/ijms-23-09698-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/d26f0a74e137/ijms-23-09698-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/0239cd80b944/ijms-23-09698-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/e43939a4465f/ijms-23-09698-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/9e0846d1d298/ijms-23-09698-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/471496580ec2/ijms-23-09698-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/0e1ea7dcebe3/ijms-23-09698-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/7a96fdc51829/ijms-23-09698-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/8edc0ffddd64/ijms-23-09698-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/2175c146e61c/ijms-23-09698-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/fca9891f4c83/ijms-23-09698-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/d26f0a74e137/ijms-23-09698-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9d31/9456463/0239cd80b944/ijms-23-09698-g009.jpg

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