Tumor targeting of functionalized quantum dot-liposome hybrids by intravenous administration.
A strategy to target functionalized quantum dot-liposome (f-QD-L) hybrid vesicles in the solid tumor tissue of tumor-bearing mice is explored. Functionalized polyethylene glycol (PEG)-lipid coated QD (f-QD) were encapsulated into the aqueous core of 100 nm cationic (DOPC:Chol: DOTAP); sterically stabilized, fluid-phase (DOPC:Chol:DSPE-PEG2000); and sterically stabilized, gel-phase (DSPC:Chol:DSPE-PEG2000) liposome vesicles. Double tracking of f-QD-L in blood was performed at different time points after intravenous administration in B16F10 melanoma tumor-bearing C57BL6 mice. Cholesteryl [-1-14C] oleate lipids probed the vesicle membrane were followed by liquid scintillation counting while QD were determined independently by elemental (Cd2+) analysis using inductively coupled plasma mass spectrometry (ICP-MS). Rapid blood clearance was observed following intravenous administration of the cationic hybrid vesicles, while incorporation of PEG at the surface of zwitterionic vesicles dramatically prolonged their blood circulation half-life after systemic administration. The "rigid" PEGylated f-QD-L (DSPC:Chol:DSPE-PEG2000) hybrid vesicles led to rapid tumor accumulation of peak values (approximately 5% of injected dose per gram tissue) of QD compared to long-circulating f-QD that accumulated in the tumor tissue at longer time points. More interestingly, this hybrid vesicle tumor retention persisted for at least 24 h. For almost all types of systems, a preferential cadmium uptake by liver and spleen was obtained. Overall, f-QD-L hybrid vesicles offer great potential for tumor imaging applications due to their rapid accumulation and prolonged retention within the tumor. Furthermore, f-QD-L offer many opportunities for the development of combinatory therapeutic and imaging (theranostic) modalities by incorporating both drug molecules and QD within the different compartments of a single vesicle.
Al-Jamal
Wafa T
WT
Nanomedicine Laboratory, Centre for Drug Delivery Research, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N lAX, UK.
Al-Jamal
Khuloud T
KT
Tian
Bowen
B
Cakebread
Andrew
A
Halket
John M
JM
Kostarelos
Kostas
K
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004337:Drug Carriers / Q000493:pharmacokinetics*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles; D011092:Polyethylene Glycols; D045663:Quantum Dots; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D011092:Polyethylene Glycols