Lipid-quantum dot bilayer vesicles enhance tumor cell uptake and retention in vitro and in vivo.
We report the construction of lipid-quantum dot (L-QD) bilayer vesicles by incorporation of the smallest (2 nm core size) commercially available CdSe/ZnS QD within zwitterionic dioleoylphosphatidylcholine and cationic 1,2-dioleoyl-3-trimethylammonium-propane lipid bilayers, self-assembling into small unilamellar vesicles. The incorporation of QD in the acyl environment of the lipid bilayer led to significant enhancement of their optical stability during storage and exposure to UV irradiation compared to that of QD alone in toluene. Moreover, structural characterization of L-QD hybrid bilayer vesicles using cryogenic electron microscopy revealed that the incorporation of QD takes place by hydrophobic self-association within the biomembranes. The L-QD vesicles bound and internalized in human epithelial lung cells (A549), and confocal laser scanning microscopy studies indicated that the L-QD were able to intracellularly traffick inside the cells. Moreover, cationic L-QD vesicles were injected in vivo intratumorally, leading to enhanced retention within human cervical carcinoma (C33a) xenografts. The hybrid L-QD bilayer vesicles presented here are thought to constitute a novel delivery system that offers the potential for transport of combinatory therapeutic and diagnostic modalities to cancer cells in vitro and in vivo.
Al-Jamal
Wafa' T
WT
Nanomedicine Lab, Centre for Drug Delivery Research, The School of Pharmacy, University of London, London WC1N 1AX, United Kingdom.
Al-Jamal
Khuloud T
KT
Tian
Bowen
B
Lacerda
Lara
L
Bomans
Paul H
PH
Frederik
Peter M
PM
Kostarelos
Kostas
K
D000818:Animals; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008051:Lipid Bilayers / Q000493:pharmacokinetics*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D045663:Quantum Dots; D014018:Tissue Distribution; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*
D004337:Drug Carriers; D008051:Lipid Bilayers