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Photothermal/matrix metalloproteinase-2 dual-responsive gelatin nanoparticles for breast cancer treatment

Xiaojie ChenCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaJiafeng ZouCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaKe ZhangCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaJingjing ZhuCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaYue ZhangCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaZhihong ZhuCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaHongyue ZhengLibraries of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaFanzhu LiCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, ChinaJi‐Gang PiaoCollege of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China
2020en
ABI

Аннотация

The chemotherapy combined with photothermal therapy has been a favorable approach for the treatment of breast cancer. In present study, nanoparticles with the characteristics of photothermal/matrix metalloproteinase-2 (MMP-2) dual-responsive, tumor targeting, and size-variability were designed for enhancing the antitumor efficacy and achieving “on-demand” drug release markedly. Based on the thermal sensitivity of gelatin, we designed a size-variable gelatin nanoparticle (GNP) to encapsulate indocyanine green (ICG) and doxorubicin (DOX). Under an 808 nm laser irradiation, GNP-DOX/ICG responded photothermally and swelled in size from 71.58 ± 4.28 to 160.80 ± 9.51 nm, which was beneficial for particle retention in the tumor sites and release of the loaded therapeutics. Additionally, GNP-DOX/ICG showed a size reduction of the particles to 33.24 ± 4.11 nm and further improved drug release with the degradation of overexpressed MMP-2 in tumor. In the subsequently performed in vitro experiments, it was confirmed that GNP-DOX/ICG could provide a therapeutic effect that was enhanced and synergistic. Consequently, GNP-DOX/ICG could efficiently suppress the growth of 4T1 tumor in vivo. In conclusion, this study may provide a promising strategy in the rational design of drug delivery nanosystems based on gelatin for chemo-photothermal therapy to achieve synergistically enhanced therapeutic efficacy against breast cancer.

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