title: Asymmetric cationic liposomes designed for heat-activated association with cells.
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.
authors.affiliation: Department of Applied Physics, Chalmers University of Technology, SE-412 96 Göteborg, Sweden; Department of Signals and Systems, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Jing
authors.affiliation: Sahlgrenska Cancer Center, Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, SE-405 30 Göteborg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Danielsson
authors.affiliation: Department of Signals and Systems, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
authors.forename: Hana Dobšíček
authors.initials: HD
authors.lastname: Trefná
authors.affiliation: Department of Signals and Systems, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Persson
authors.affiliation: Department of Applied Physics, Chalmers University of Technology, SE-412 96 Göteborg, Sweden. Electronic address: sofia.svedhem@chalmers.se.
authors.forename: Sofia
authors.initials: S
authors.lastname: Svedhem
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002277:Carcinoma / Q000378:metabolism; D002412:Cations; D045744:Cell Line, Tumor / Q000187:drug effects; D004396:Coloring Agents / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005334:Fever / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D050866:Liquid Crystals / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry; D009369:Neoplasms / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism; D010316:Particle Size; D044367:Phase Transition; D011092:Polyethylene Glycols / Q000737:chemistry; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D004396:Coloring Agents; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D008563:Membrane Lipids; D011092:Polyethylene Glycols
keywords: Cationic liposomes; Cellular uptake; Hyperthermia; Membrane asymmetry; PEGylation