Tumor targeting of functionalized quantum dot-liposome hybrids by intravenous administration.

Al-Jamal, W.T., Al-Jamal, K.T., Tian, B., Cakebread, A., Halket, J.M. and Kostarelos, K. (2009) Tumor targeting of functionalized quantum dot-liposome hybrids by intravenous administration. Molecular Pharmaceutics, 6 (2). pp. 520-530. 10.1021/mp800187d.

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DOI: 10.1021/mp800187d

Abstract

A strategy to target functionalized quantum d0t-liposome (f-QD-L) hybrid vesicles in the solid tumor tissue of tumor-bearing mice is explored. Functionalized poluethylene glycol (PEG)-lipid coated QD (f-QD) were encapsulated into the aqueous core of 100 mn cationic (DOPC:Chol:DOTAP); sterically stablized, 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 [-1-14C] oleate lipids probed the vesicle membrane were followed by liquid scitillation counting while QD were determined independently by elemental (Cd 2+) analysis using inductively coupled plasma mass spectrometry (ICP-MS). Rapid blood clearance was observed following intravenous administation 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 QD compared to long-circulating f-QD that accumulated in the tumor tissue at longer time points. Mre 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 combinatroy therapeutic and imaging (theranostic) modalities by incorporating both drug molecules and QD within the different compartments of a single vesicle.

Item Type:Article
Additional Information:Full text available electronically from the School of Pharmacy Library.
Departments, units and centres:Department of Pharmaceutics > Centre for Drug Delivery Research
ID Code:1244
Journal or Publication Title:Molecular Pharmaceutics
Deposited By:Library Staff
Deposited On:26 Jun 2009 15:42
Last Modified:04 May 2012 10:54

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