Reversible glycosidic switch for secure delivery of molecular nanocargos

doi:10.1038/s41467-018-04225-5

CNU IR > Pharmacy and Science > Dept. of Pharmacy > Periodical Articles > Item 310902800/32258

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Title:	Reversible glycosidic switch for secure delivery of molecular nanocargos
Authors:	Burnouf, Pierre-Alain Leu, Yu-Lin Su, Yu-Cheng Wu, Kenneth Lin, Wei-Chi Roffler, Steve R.
Contributors:	Natl Yang Ming Univ, Taiwan Int Grad Program Mol Med Acad Sinica Acad Sinica, Inst Biomed Sci Natl Yang Ming Univ, Inst Biochem & Mol Biol Chia Nan Univ Pharm & Sci, Dept Pharm Kaohsiung Med Univ, Coll Med, Grad Inst Med
Keywords:	Liposomal Drug-Delivery Cells-In-Vitro Cancer-Therapy Lipophilic Drugs Topoisomerase-I Accumulation Camptothecin Efficacy Glucuronide Prodrug
Date:	2018-05-10
Issue Date:	2019-11-15 15:47:08 (UTC+8)
Publisher:	NATURE PUBLISHING GROUP
Abstract:	Therapeutic drugs can leak from nanocarriers before reaching their cellular targets. Here we describe the concept of a chemical switch which responds to environmental conditions to alternate between a lipid-soluble state for efficient cargo loading and a water-soluble state for stable retention of cargos inside liposomes. A cue-responsive trigger allows release of the molecular cargo at specific cellular sites. We demonstrate the utility of a specific glycosidic switch for encapsulation of potent anticancer drugs and fluorescent compounds. Stable retention of drugs in liposomes allowed generation of high tumor/blood ratios of parental drug in tumors after enzymatic hydrolysis of the glycosidic switch in the lysosomes of cancer cells. Glycosidic switch liposomes could cure mice bearing human breast cancer tumors without significant weight loss. The chemical switch represents a general method to load and retain cargos inside liposomes, thereby offering new perspectives in engineering safe and effective liposomes for therapy and imaging.
Relation:	Qjm-An International Journal of Medicine, v.9, 1843
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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