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Cited 9 time in webofscience Cited 10 time in scopus
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Cancer-specific drug-drug nanoparticles of pro-apoptotic and cathepsin B-cleavable peptide-conjugated doxorubicin for drug-resistant cancer therapy

Authors
Shim, Man KyuMoon, YujeongYang, SuahKim, JinseongCho, HanheeLim, SeunghoYoon, Hong YeolSeong, Joon-KyungKim, Kwangmeyung
Issue Date
12월-2020
Publisher
ELSEVIER SCI LTD
Keywords
Drug resistance; Prodrug; Cancer nanomedicine; Synergetic effect
Citation
BIOMATERIALS, v.261
Indexed
SCIE
SCOPUS
Journal Title
BIOMATERIALS
Volume
261
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/51394
DOI
10.1016/j.biomaterials.2020.120347
ISSN
0142-9612
Abstract
Chemotherapy has shown remarkable therapeutic efficacy for various types of cancer. However, drug resistance reduces the effectiveness and sensitivity of chemotherapy, leading treatment failure and cancer relapse in many clinical indications. Herein, we propose cancer-specific drug-drug nanoparticles (DD-NPs) that improve the therapeutic efficacy of chemotherapy against drug-resistant cancer. Cancer-specific and pro-apoptotic drug-drug conjugate was prepared by conjugating the pro-apoptotic peptide drug (SMAC; Ala-Val-Pro-Ile-Ala-Gin, AVPIAQ) and cathepsin B-cleavable peptide (Phe-Arg-Arg-Gly, FRRG) to a doxorubicin (DOX), resulting in SMAC-FRRGDOX that allows self-assembled into nanoparticles. The resulting DD-NPs were specifically cleaved to proapoptotic SMAC and cytotoxic DOX only in cathepsin B-overexpressing cancer cells, inducing a synergy of the pro-apoptotic activity with the chemotherapy. In MCF-7 breast tumor-bearing mice, intravenously injected DD-NPs highly accumulated at targeted tumor tissues via enhanced permeability and retention (EPR) effect, releasing SMAC and DOX, which showed a synergetic pro-apoptotic/chemotherapy. Furthermore, DD-NPs greatly suppressed tumor growth and improved overall survival in a metastatic lung cancer model. Collectively, these cancer-specific drug-drug nanoparticles may be a promising strategy to treat drug-resistant cancers with high cancer cell-specificity.
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Graduate School > Department of Artificial Intelligence > 1. Journal Articles
Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles

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