Dequalinium-based functional nanosomes show increased mitochondria targeting and anticancer effect

European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V
Yoonhee BaeJoon Sig Choi

Abstract

Mitochondria are targets with great potential for therapeutics for many human disorders. However, drug delivery systems for such therapeutics remain in need of more efficient mitochondrial-targeting carriers. In this study, we report that nanosomes composed of Dequalinium/DOTAP (1,2-dioleoyl-3-trimethylammonium-propane)/DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine), called DQA80s, can act in the dual role of mitochondrial-targeting carrier and anticancer agent for therapeutic interventions against mitochondrial diseases. In cytotoxicity assays, DQA80s were shown to be more toxic than DQAsomes. The DQA80s showed significantly increased cellular uptake as compared to that of DQAsomes, and DQA80s also showed more efficient escape from the endolysosome to the cytosol. We observed the efficient targeting of DQA80s to mitochondria in living cells using flow cytometry, confocal microscopy, and TEM imaging. We also found evidence of anticancer potential that mitochondrial-targeted DQA80s induced apoptosis by production of reactive oxygen species (ROS) via MAPK signaling pathways, loss of mitochondrial membrane potential, and the caspase-3 activation. The present study demonstrates that DQA80s have excellent dual potential both a...Continue Reading

Citations

Sep 4, 2018·Frontiers in Pharmacology·Gantumur BattogtokhHan Chang Kang
Mar 4, 2020·Current Pharmaceutical Design·Igor A Sobenin, Vasily N Sukhorukov
Dec 18, 2019·BMC Cancer·Tarek ZaidiehQian An
Jan 27, 2021·Clinical and Experimental Pharmacology & Physiology·Yuehai PanFan Chen
Feb 13, 2021·Biochemical Pharmacology·Christian Bailly
Nov 26, 2019·Current Medicinal Chemistry·Olakunle OladimejiMoganavelli Singh
Jun 18, 2021·International Journal of Nanomedicine·Khaled S AllemailemAmjad Ali Khan
Dec 31, 2021·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Yoonhee BaeJin Han

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