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Mitochondria-targeted delivery of doxorubicin to enhance antitumor activity with HER-2 peptide-mediated multifunctional pH-sensitive DQAsomes

Authors Shi M, Zhang J, Li X, Pan S, Li J, Yang C, Hu H, Qiao M, Chen D, Zhao X

Received 26 January 2018

Accepted for publication 24 April 2018

Published 18 July 2018 Volume 2018:13 Pages 4209—4226

DOI https://doi.org/10.2147/IJN.S163858

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Alexander Kharlamov

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Menghao Shi,1 Jiulong Zhang,1 Xiaowei Li,1 Shuang Pan,1 Jie Li,2 Chunrong Yang,3 Haiyang Hu,1 Mingxi Qiao,1 Dawei Chen,1 Xiuli Zhao1

1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, People’s Republic of China; 2Department of Pharmacy, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, People’s Republic of China; 3College Pharmacy of Jiamusi University, Jiamusi, Heilongjiang 154007, People’s Republic of China

Introduction: Multidrug resistance (MDR) of breast cancer is the major challenge to successful chemotherapy while mitochondria-targeting therapy was a promising strategy to overcome MDR.
Materials and methods: In this study, HER-2 peptide-PEG2000-Schiff base-cholesterol (HPSC) derivate was synthesized successfully and incorporated it on the surface of the doxorubicin (DOX)-loaded dequalinium (DQA) chloride vesicle (HPS-DQAsomes) to treat drug-resistant breast cancer. Evaluations were performed using human breast cancer cell and DOX-resistant breast cancer cell lines (MCF-7 and MCF-7/ADR).
Results: The particle size of HPS-DQAsomes was ~110 nm with spherical shape. In vitro cytotoxicity assay indicated that HPS-DQAsomes could increase the cytotoxicity against MCF-7/ADR cell line. Cellular uptake and mitochondria-targeting assay demonstrated that HPS-DQAsomes could target delivering therapeutical agent to mitochondria and inducing mitochondria-driven apoptosis process. In vivo antitumor assay suggested that HPS-DQAsomes could reach favorable antitumor activity due to both tumor targetability and sub-organelles’ targetability. Histological assay also indicated that HPS-DQAsomes showed a strong apoptosis-inducing effect. No obvious systematic toxicity of HPS-DQAsomes could be observed.
Conclusion: In summary, multifunctional HPS-DQAsomes provide a novel and versatile approach for overcoming MDR via mitochondrial pathway in cancer treatment.

Keywords: mitochondrial target, DQAsomes, pH responsive, HER-2 peptide

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