Heat-activated liposome targeting to streptavidin-coated surfaces.
There is a great need of improved anticancer drugs and corresponding drug carriers. In particular, liposomal drug carriers with heat-activated release and targeting functions are being developed for combined hyperthermia and chemotherapy treatments of tumors. The aim of this study is to demonstrate the heat-activation of liposome targeting to biotinylated surfaces, in model experiments where streptavidin is used as a pretargeting protein. The design of the heat-activated liposomes is based on liposomes assembled in an asymmetric structure and with a defined phase transition temperature. Asymmetry between the inside and the outside of the liposome membrane was generated through the enzymatic action of phospholipase D, where lipid head groups in the outer membrane leaflet, i.e. exposed to the enzyme, were hydrolyzed. The enzymatically treated and purified liposomes did not bind to streptavidin-modified surfaces. When activation heat was applied, starting from 22°C, binding of the liposomes occurred once the temperature approached 33±0.5°C. Moreover, it was observed that the asymmetric structure remained stable for at least 2 weeks. These results show the potential of asymmetric liposomes for the targeted binding to cell membranes in response to (external) temperature stimulus. By using pretargeting proteins, this approach can be further developed for personalized medicine, where tumor-specific antibodies can be selected for the conjugation of pretargeting agents.
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.
Yujia
Y
Jing
Department of Signals and Systems, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
Hana Dobšíček
HD
Trefná
Department of Signals and Systems, Chalmers University of Technology, SE-412 96 Göteborg, Sweden.
Mikael
M
Persson
Department of Applied Physics, Chalmers University of Technology, SE-412 96 Göteborg, Sweden. Electronic address: sofia.svedhem@chalmers.se.
Sofia
S
Svedhem
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D001710:Biotin / Q000737:chemistry; D006358:Hot Temperature; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D019809:Streptavidin / Q000737:chemistry*; D013499:Surface Properties
D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D010714:Phosphatidylethanolamines; D015060:1,2-Dipalmitoylphosphatidylcholine; C007510:1,2-dipalmitoyl-3-phosphatidylethanolamine; D001710:Biotin; D019809:Streptavidin
Membrane asymmetry; Phospholipase D; Targeting; Temperature-responsive