期刊
MOLECULAR PHARMACEUTICS
卷 6, 期 2, 页码 520-530出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp800187d
关键词
Quantum dots; liposomes; hybrid; biodistribution; tumor targeting; pharmacokinetics; ICP-MS
资金
- Overseas Research Student Award Scheme (ORSAS)
- University of London
- Maplethorpe Fellowship, The University of London
A strategy to target functionalized quantum clot-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-PEG(2000)); and sterically stabilized, gel-phase (DSPC:Chol:DSPE-PEG(2000)) 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-C-14] oleate lipids probed the vesicle membrane were followed by liquid scintillation counting while OD 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-PEG(2000)) hybrid vesicles led to rapid tumor accumulation of peak values (approximately 5% of injected dose per gram tissue) of OD 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.
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