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Inhibition of growth and lung metastasis of breast cancer by tumor-homing triple-bioresponsive nanotherapeutics.

Authors
  • Zhang, Xueqing1
  • Huang, Yamei1
  • Song, Heliang2
  • Canup, Brandon S B2
  • Gou, Shuangquan1
  • She, Zhigang3
  • Dai, Fangyin4
  • Ke, Bowen5
  • Xiao, Bo6
  • 1 State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University, Beibei, Chongqing 400715, PR China. , (China)
  • 2 Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA. , (Georgia)
  • 3 Medical Research Institute, School of Medicine, Wuhan University, Wuhan, Hubei 430071, PR China. , (China)
  • 4 State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University, Beibei, Chongqing 400715, PR China; Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Southwest University, Beibei, Chongqing 400715, PR China. Electronic address: [email protected] , (China)
  • 5 Laboratory of Anesthesiology & Critical Care Medicine, Department of Anesthesiology, Translational Neuroscience Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 61004, PR China. Electronic address: [email protected] , (China)
  • 6 State Key Laboratory of Silkworm Genome Biology, School of Materials and Energy, Southwest University, Beibei, Chongqing 400715, PR China; Key Laboratory of Sericultural Biology and Genetic Breeding, Ministry of Agriculture and Rural Affairs, College of Sericulture, Textile and Biomass Sciences, Southwest University, Beibei, Chongqing 400715, PR China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Journal of controlled release : official journal of the Controlled Release Society
Publication Date
Sep 03, 2020
Volume
328
Pages
454–469
Identifiers
DOI: 10.1016/j.jconrel.2020.08.066
PMID: 32890553
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Lung metastasis of breast cancer is a leading cause of cancer-related death in women. Herein, we attempted to simultaneously inhibit the growth and lung metastasis of breast cancer by delivering quercetin (QU) using LyP-1-functionalized regenerated silk fibroin-based nanoparticles (NPs). The generated LyP-1-QU-NPs had a desirable diameter (203.2 nm) and a negatively charged surface (-12.7 mV). Interestingly, these NPs exhibited intrinsic responsibilities when triggered by various stimulating factors in the tumor microenvironment (acidic pH, reactive oxygen species, and glutathione). In vitro experiments revealed that the introduction of LyP-1 to the NP surface could significantly increase their cellular uptake efficiencies by 4 T1 cells, and facilitate their accumulation in mitochondria. Moreover, LyP-1-QU-NPs showed the strongest mitochondrial damage effect among all the treatment groups. We also found that LyP-1-QU-NPs not only exhibited excellent pro-apoptotic activities but also presented strong inhibitory effects on cell mobility (migration and invasion) through anti-glycolysis and pro-autophagy. Mice experiments confirmed that LyP-1-QU-NPs could efficiently inhibit the in situ growth of breast tumors and further restrict their lung metastasis. Collectively, our results demonstrate that LyP-1-QU-NPs, which integrates the functions of tumor cell targeting, mitochondria targeting, bioresponsive drug release, pro-apoptosis, and anti-mobility, can be developed as a promising nanotherapeutic for the effective treatment of breast cancer and its lung metastasis. Copyright © 2020 Elsevier B.V. All rights reserved.

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