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

Wafa T Al-Jamal, Khuloud T Al-Jamal, Bowen Tian, Andrew Cakebread, John M Halket, Kostas Kostarelos

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)520-30
Number of pages11
JournalMolecular Pharmaceutics
Volume6
Issue number2
DOIs
Publication statusPublished - 01 Sep 2009
Externally publishedYes

Keywords

  • Animals
  • Antineoplastic Agents
  • Drug Carriers
  • Lipids
  • Liposomes
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles
  • Polyethylene Glycols
  • Quantum Dots
  • Tissue Distribution
  • Journal Article
  • Research Support, Non-U.S. Gov't

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