la202679p_si_001.pdf (377.06 kB)
Silica-Coated Quantum Dots for Optical Evaluation of Perfluorocarbon Droplet Interactions with Cells
journal contribution
posted on 2011-12-20, 00:00 authored by Ivan Gorelikov, Amanda
L. Martin, Minseok Seo, Naomi MatsuuraThere has been recent interest in developing new, targeted, perfluorocarbon
(PFC) droplet-based contrast agents for medical imaging (e.g., magnetic
resonance imaging, X-ray/computed tomography, and ultrasound imaging).
However, due to the large number of potential PFCs and droplet stabilization
strategies available, it is challenging to determine in advance the
PFC droplet formulation that will result in the optimal in
vivo behavior and imaging performance required for clinical
success. We propose that the integration of fluorescent quantum dots
(QDs) into new PFC droplet agents can help to rapidly screen new PFC-based
candidate agents for biological compatibility early in their development.
QD labels can allow the interaction of PFC droplets with single cells
to be assessed at high sensitivity and resolution using optical methods in vitro, complementing the deeper depth penetration but
lower resolution provided by PFC droplet imaging using in
vivo medical imaging systems. In this work, we introduce
a simple and robust method to miscibilize silica-coated nanoparticles
into hydrophobic and lipophobic PFCs through fluorination of the silica
surface via a hydrolysis-condensation reaction with 1H,1H,2H,2H-perfluorodecyltriethoxysilane.
Using CdSe/ZnS core/shell QDs, we show that nanoscale, QD-labeled
PFC droplets can be easily formed, with similar sizes and surface
charges as unlabeled PFC droplets. The QD label can be used to determine
the PFC droplet uptake into cells in vitro by fluorescence
microscopy and flow cytometry, and can be used to validate the fate
of PFC droplets in vivo in small animals via fluorescence
microscopy of histological tissue sections. This is demonstrated in
macrophage and cancer cells, and in rabbits, respectively. This work
reveals the potential of using QD labels for rapid, preclinical, optical
assessment of different PFC droplet formulations for their future
use in patients.