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

• Main Authors: Shi M, Zhang J, Li X, Pan S, Li J, Yang C, Hu H, Qiao M, Chen D, Zhao X
• Format: Article
• Language: English
• Published: Dove Medical Press 2018-07-01
• Series: International Journal of Nanomedicine
• Subjects: mitochondrial target; DQAsomes; pH-responsive; HER-2 peptide
• Online Access: https://www.dovepress.com/mitochondria-targeted-delivery-of-doxorubicin-to-enhance-antitumor-act-peer-reviewed-article-IJN

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