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一种用于高效治疗耐多柔比星乳腺癌的谷胱甘肽/壳聚糖双控自组装纳米药物

A GSH/CB Dual-Controlled Self-Assembled Nanomedicine for High-Efficacy Doxorubicin-Resistant Breast Cancer Therapy.

作者信息

Yang Yang, Zhao Quanfeng, Peng Zhe, Zhou Yunjiang, Niu Miao-Miao, Chen Lin

机构信息

Department of Pharmacology, Chongqing Health Center for Women and Children, Chongqing, China.

Department of Pharmacy, Southwest Hospital, First Affiliated Hospital to TMMU, Third Military Medical University (Army Medical University), Chongqing, China.

出版信息

Front Pharmacol. 2022 Jan 14;12:811724. doi: 10.3389/fphar.2021.811724. eCollection 2021.

DOI:10.3389/fphar.2021.811724
PMID:35095524
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8795745/
Abstract

Chemoresistance is a major therapeutic obstacle in the treatment of breast cancer. Therefore, how to overcome chemoresistance is a problem to be solved. Here, a glutathione (GSH)/cathepsin B (CB) dual-controlled nanomedicine formed by cyclic disulfide-bridged peptide (cyclic-1a) as a potent anticancer agent is reported. Under the sequential treatment of GSH and CB, cyclic-1a can efficiently self-assemble into nanofibers. studies show that cyclic-1a promotes the apoptosis of MCF-7/DOX cells by inducing the cleavages of caspase-3 and PARP. studies confirm that cyclic-1a significantly inhibits the progression of MCF-7/DOX cells-derived xenograft in nude mice, with no obvious adverse reactions. This study provides a paradigm of GSH/CB dual-controlled nanomedicine for high-efficacy and low-toxic DOX-resistant breast cancer therapy.

摘要

化疗耐药是乳腺癌治疗中的主要治疗障碍。因此，如何克服化疗耐药是一个亟待解决的问题。在此，报道了一种由环状二硫键桥联肽（环状-1a）作为强效抗癌剂形成的谷胱甘肽（GSH）/组织蛋白酶B（CB）双控纳米药物。在GSH和CB的顺序处理下，环状-1a能有效地自组装成纳米纤维。研究表明，环状-1a通过诱导caspase-3和PARP的裂解促进MCF-7/DOX细胞凋亡。研究证实，环状-1a显著抑制MCF-7/DOX细胞衍生的裸鼠异种移植瘤的进展，且无明显不良反应。本研究为高效低毒的耐多柔比星乳腺癌治疗提供了一种GSH/CB双控纳米药物的范例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/1ceca3f12d3a/fphar-12-811724-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/85f063a6b630/fphar-12-811724-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/477205473646/fphar-12-811724-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/892537359072/fphar-12-811724-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/33daab51a8ad/fphar-12-811724-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/e05042ef9531/fphar-12-811724-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/1ceca3f12d3a/fphar-12-811724-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/85f063a6b630/fphar-12-811724-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/477205473646/fphar-12-811724-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/892537359072/fphar-12-811724-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/33daab51a8ad/fphar-12-811724-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/e05042ef9531/fphar-12-811724-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b2e2/8795745/1ceca3f12d3a/fphar-12-811724-g006.jpg

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引用本文的文献

[1]
Cancer-associated fibroblasts promote doxorubicin resistance in triple-negative breast cancer through enhancing ZFP64 histone lactylation to regulate ferroptosis.

J Transl Med. 2025-2-28

[2]
Commentary: A GSH/CB dual-controlled self-assembled nanomedicine for high-efficacy doxorubicin-resistant breast cancer therapy.

Front Pharmacol. 2022-11-28

本文引用的文献

[1]
SAPdb: A database of short peptides and the corresponding nanostructures formed by self-assembly.

Comput Biol Med. 2021-6

[2]
An NRP1/MDM2-Targeted D-Peptide Supramolecular Nanomedicine for High-Efficacy and Low-Toxic Liver Cancer Therapy.

Adv Healthc Mater. 2021-5

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Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.

CA Cancer J Clin. 2021-5

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Biomolecules. 2020-10-9

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Cancer-specific drug-drug nanoparticles of pro-apoptotic and cathepsin B-cleavable peptide-conjugated doxorubicin for drug-resistant cancer therapy.

Biomaterials. 2020-12

[7]
Re: Hanbing Song, Bobak Seddighzadeh, Matthew R. Cooperberg, Franklin W. Huang. Expression of ACE2 and TMPRSS2, the SARS-CoV-2 Receptor and Co-Receptor, in Prostate Epithelial Cells. Eur Urol. In press DOI: 10.1016/j.eururo.2020.04.065.

Eur Urol. 2020-11

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Dual Single-Atomic Ni-N and Fe-N Sites Constructing Janus Hollow Graphene for Selective Oxygen Electrocatalysis.

Adv Mater. 2020-7

[9]
A single-step multi-level supramolecular system for cancer sonotheranostics.

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Mitochondrial Determinants of Doxorubicin-Induced Cardiomyopathy.

Circ Res. 2020-3-26

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