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

International Journal of Nanomedicine
Menghao ShiXiuli Zhao

Abstract

Multidrug resistance (MDR) of breast cancer is the major challenge to successful chemotherapy while mitochondria-targeting therapy was a promising strategy to overcome MDR. 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). 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 ...Continue Reading

Citations

Jul 16, 2020·Gastroenterology Report·Yaritza Delgado-DeidaArianne L Theiss
Jun 23, 2019·International Journal of Molecular Sciences·Shar-Yin Naomi Huang, Yves Pommier
Feb 4, 2021·APL Bioengineering·Matthew R AronsonMichael J Mitchell
Feb 13, 2021·Biochemical Pharmacology·Christian Bailly
Dec 12, 2020·Saudi Journal of Biological Sciences·Sugapriya DhanasekaranArif Ahmed Mohammed
Nov 17, 2020·Bioconjugate Chemistry·Cindy MaShana O Kelley
May 24, 2021·Journal of Photochemistry and Photobiology. B, Biology·Yunsu MaDongzhi Yang
Jun 28, 2021·Nanomedicine : Nanotechnology, Biology, and Medicine·Lara MilaneMansoor Amiji
Jun 25, 2021·International Journal of Nanomedicine·Yongjia HuangJingqing Zhang

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Methods Mentioned

BETA
transmission electron microscopy
fluorescence
fluorescence microscopy
flow cytometry
xenograft

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