Tumor Targeting of Functionalized Quantum Dot−Liposome Hybrids by Intravenous Administration

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.

Quantum dots: bright and versatile in vitro and in vivo fluorescence imaging biosensors

“…The longer circulation time also led to a higher accumulation in the tumour. 409 These results were supported by Papagiannaros and coworkers, who used QDs encapsulated in PEG-phospholipid micelles. Compared to commercially available QD-PEG they accumulated much faster (1 h instead of 4 h) and only half of the dosage was necessary to reach the same SNR.…”

Toward Biocompatible Semiconductor Quantum Dots: From Biosynthesis and Bioconjugation to Biomedical Application

“…Furthermore, Kostarelos and colleagues constructed a series of liposome-QD hybrids for diagnostic and therapeutic applications. 181,540,542,567,568 Their research reveals that the lipid composition and bilayer characteristics of liposome-QD hybrid vesicles may significantly affect their stability in blood, in vivo pharmacological behavior, and tissue biodistribution profile. 567,568 Brinker and colleague prepared a porous nanoparticle-supported lipid bilayer (protocell) with the features of both liposomes and mesoporous silica nanoparticles (MSNs).…”

“…181,540,542,567,568 Their research reveals that the lipid composition and bilayer characteristics of liposome-QD hybrid vesicles may significantly affect their stability in blood, in vivo pharmacological behavior, and tissue biodistribution profile. 567,568 Brinker and colleague prepared a porous nanoparticle-supported lipid bilayer (protocell) with the features of both liposomes and mesoporous silica nanoparticles (MSNs). 541 This multifunctional protocell significantly improves loading capacity, target selectivity, stability, and controlled drug release, facilitating the targeted delivery of multicomponent cargo into cancer cells.…”

Chemically engineered persistent luminescence nanoprobes for bioimaging

“…Thus, this type of PLNPs do not enable for example in vivo tumour homing strategies such as those relying on slow accumulation of stealth nanocarriers within malignant stroma by the enhanced permeability and retention effect 78,79. Depending on the nanoparticle characteristics, such retention processes usually require from 2 to 24 hours 80,81. This is far too long in relation to the emission from PLNPs, which hardly exceeds 1 to 3 hours in vivo .…”