posted on 2020-01-09, 18:07authored bySangwoo Park, Jae Won Ahn, YoungJu Jo, Ha-Young Kang, Hyun Jung Kim, Yeongmi Cheon, Jin Won Kim, YongKeun Park, Seongsoo Lee, Kyeongsoon Park
Lipid
droplet (LD) accumulation, a key feature of foam cells, constitutes
an attractive target for therapeutic intervention in atherosclerosis.
However, despite advances in cellular imaging techniques, current
noninvasive and quantitative methods have limited application in living
foam cells. Here, using optical diffraction tomography (ODT), we performed
quantitative morphological and biophysical analysis of living foam
cells in a label-free manner. We identified LDs in foam cells by verifying
the specific refractive index using correlative imaging comprising
ODT integrated with three-dimensional fluorescence imaging. Through
time-lapse monitoring of three-dimensional dynamics of label-free
living foam cells, we precisely and quantitatively evaluated the therapeutic
effects of a nanodrug (mannose–polyethylene glycol–glycol
chitosan–fluorescein isothiocyanate–lobeglitazone; MMR-Lobe)
designed to affect the targeted delivery of lobeglitazone to foam
cells based on high mannose receptor specificity. Furthermore, by
exploiting machine-learning-based image analysis, we further demonstrated
therapeutic evaluation at the single-cell level. These findings suggest
that refractive index measurement is a promising tool to explore new
drugs against LD-related metabolic diseases.