Functionalized-quantum-dot-liposome (f-QD-L) hybrid nanoparticles are engineered by encapsulating poly(ethylene glycol)-coated QD in the internal aqueous phase of different lipid bilayer vesicles. f-QD-L maintain the QD fluorescence characteristics as confirmed by fluorescence spectroscopy, agarose gel electrophoresis, and confocal laser scanning microscopy. Cationic f-QD-L hybrids lead to dramatic improvements in cellular binding and internalization in tumor-cell monolayer cultures. Deeper penetration into three-dimensional multicellular spheroids is obtained for f-QD-L by modifying the lipid bilayer characteristics of the hybrid system. f-QD-L are injected intratumorally into solid tumor models leading to extensive fluorescent staining of tumor cells compared to injections of the f-QD alone. f-QD-L hybrid nanoparticles constitute a versatile tool for very efficient labeling of cells ex vivo and in vivo, particularly when long-term imaging and tracking of cells is sought. Moreover, 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. ; Times Cited: 64 0 65