11 research outputs found
Dendritic Polyglycerolsulfate Near Infrared Fluorescent (NIRF) Dye Conjugate for Non-Invasively Monitoring of Inflammation in an Allergic Asthma Mouse Model
Background: Non-invasive in vivo imaging strategies are of high demand for longitudinal monitoring of inflammation
during disease progression. In this study we present an imaging approach using near infrared fluorescence (NIRF) imaging
in combination with a polyanionic macromolecular conjugate as a dedicated probe, known to target L- and P-selectin and
C3/C5 complement factors.
Methodology/Principal Findings: We investigated the suitability of dendritic polyglycerol sulfates (dPGS), conjugated with
a hydrophilic version of the indocyanine green label with 6 sulfonate groups (6S-ICG) to monitor sites of inflammation using
an experimental mouse model of allergic asthma. Accumulation of the NIRF-conjugated dPGS (dPGS-NIRF) in the inflamed
lungs was analyzed in and ex vivo in comparison with the free NIRF dye using optical imaging. Commercially available smart
probes activated by matrix metalloproteinase’s (MMP) and cathepsins were used as a comparative control. The fluorescence
intensity ratio between lung areas of asthmatic and healthy mice was four times higher for the dPGS in comparison to the
free dye in vivo at four hrs post intravenous administration. No significant difference in fluorescence intensity between
healthy and asthmatic mice was observed 24 hrs post injection for dPGS-NIRF. At this time point ex-vivo scans of asthmatic
mice confirmed that the fluorescence within the lungs was reduced to approximately 30% of the intensity observed at 4 hrs
post injection.
Conclusions/Significance: Compared with smart-probes resulting in a high fluorescence level at 24 hrs post injection
optical imaging with dPGS-NIRF conjugates is characterized by fast uptake of the probe at inflammatory sites and
represents a novel approach to monitor lung inflammation as demonstrated in mice with allergic asthma.peerReviewe