Functionalized-Quantum-Dot-Liposome Hybrids as Multimodal Nanoparticles for Cancer

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 4; no. 9; pp. 1406 - 1415
• Main Authors: Al-Jamal, Wafa' T., Al-Jamal, Khuloud T., Bomans, Paul H., Frederik, Peter M., Kostarelos, Kostas
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.09.2008; WILEY‐VCH Verlag
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - therapeutic use; Cell Line; Cryoelectron Microscopy; Female; liposomes; Liposomes - chemistry; Mice; Mice, Inbred C57BL; Microscopy, Electron, Transmission; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Nanoparticles - ultrastructure; Neoplasm Transplantation; Neoplasms - drug therapy; Neoplasms - pathology; Particle Size; Quantum Dots; Spectrometry, Fluorescence; spheroid penetration; Surface Properties; theranostics; tumor imaging
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.200701043

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. Functionalized quantum‐dot–liposome (f‐QD‐L) hybrids are engineered by encapsulation of fluorescent poly(ethylene glycol)‐coated QD in the internal aqueous phase of lipid vesicles (see image). Cationic f‐QD‐L hybrids have shown dramatic improvements in cellular binding and deeper penetration into three‐dimensional multicellular tumor spheroids, without the need for conjugation chemistry on the QD surface.