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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
Keywords Cationic liposomes, Cellular uptake, Hyperthermia, Membrane asymmetry, PEGylation
Subject categories Cancer and Oncology


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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