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Asymmetric cationic liposomes designed for heat-activated association with cells

Journal article
Authors Y. Jing
Anna Danielsson
H. D. Trefná
M. Persson
S. Svedhem
Published in Colloids and Surfaces B: Biointerfaces
Volume 151
Pages 112-118
ISSN 0927-7765
Publication year 2017
Published at Institute of Clinical Sciences, Department of Oncology
Sahlgrenska Cancer Center
Pages 112-118
Language en
Links dx.doi.org/10.1016/j.colsurfb.2016....
Keywords Cationic liposomes, Cellular uptake, Hyperthermia, Membrane asymmetry, PEGylation
Subject categories Cancer and Oncology

Abstract

Improved anticancer drugs and drug carriers are needed in combination therapies, such as hyperthermia-assisted chemotherapy. Liposomal drug carriers with advanced functions are attractive candidates for targeted accumulation and drug release in response to heat stimulus. We report on the design of liposomes with a heat-activated surface function. Our design is based on asymmetric lipid membranes with a defined gel to liquid-crystalline phase-transition temperature around 41 °C. Asymmetry between the inner and the outer membrane leaflets was generated through selective PEGylation of cationic lipids in the outer membrane leaflet. In a physiological buffer, the PEGylated asymmetric liposomes had a neutral zeta potential and did not bind to planar anionic model membranes. In contrast, following upon heat-activation, binding of liposomes to the model membranes occurred. Release of a hydrophilic dye encapsulated in the asymmetric liposomes occurred at 40 °C. Enhanced uptake of the asymmetric liposomes by hypopharyngeal carcinoma cells (FaDu cells) was observed when hyperthermia was applied compared to experiments performed at 37 °C. These results show the potential of asymmetric liposomes for localized delivery of drugs into cells in response to (external) temperature stimulus. © 2016

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