Given that apoptosis increases the risk of plaque
rupture, strategies that reduce intracellular
lipid levels without killing foam cells are warranted for safe and effective treatment of
atherosclerosis. In this study, a mild
phototherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow
photothermal therapy (PTT) and/or
photodynamic therapy (
PDT) were prepared by loading
hyaluronan and
porphine onto black TiO2 nanoparticles. The results showed that when temperatures below 45 °C, PTT alone and PTT + PDT significantly reduced the intracellular
lipid burden without inducing evidently apoptosis or
necrosis. In contrast, the use of
PDT alone resulted in only a slight reduction in
lipid levels and induced massive apoptosis or
necrosis. The protective effect against apoptosis or
necrosis after mild-temperature PTT and PTT + PDT was correlated with the upregulation of
heat shock protein 27. Further, mild-temperature PTT and PTT + PDT attenuated intracellular
cholesterol biosynthesis and excess
cholesterol uptake via the SREBP2/LDLR pathway, and also triggered ABCA1-mediated
cholesterol efflux, ultimately inhibiting
lipid accumulation in foam cells. Our results offer new insights into the mechanism of
lipid regulation in foam cells and indicate that the black TiO2 nanoprobes could allow safer and more effective
phototherapy of
atherosclerosis.