Black TiO_(2) nanoprobe-mediated mild phototherapy reduces intracellular lipid levels in atherosclerotic foam cells via cholesterol regulation pathways instead of apoptosis

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 pho-totherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow photo-thermal therapy (PTT) and/or photodynamic therapy (PDT) were prepared by loading hyaluronan and porphine onto black TiO_(2) 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 TiO_(2) nanoprobes could allow safer and more effective phototherapy of atherosclerosis.

Polydopamine nanoparticle-mediated mild photothermal therapy for inhibiting atherosclerotic plaque progression by regulating lipid metabolism of foam cells

Since apoptosis of foam,cells can induce plaque instability,reducing intracellular lipid content while protecting foam cells from apoptosis is beneficial for the safe and efficient therapy of atherosclerosis.In this study,osteopontin-coupled polydopamine(PDA-OPN)nanoparticles were synthesized and applied to target mild photothermal therapy(PTT)of atherosclerosis.The results from laser confocal microscopy indicate that PDA-OPN nanoparticles can be specially recognized and absorbed by foam cells.Under near-infrared laser irradiation,the mild photothermal generated by PDA-OPN decreases intracellular lipid accumulation but does not induce cell apoptosis.In vivo treatments demonstrate that mild PTT can substantially reduce plaque area and improve plaque stability by upregulating the expression of plaque fibrosis in ApoE^(−/−)mice.Our findings reinforce that the PDA-OPN nanoparticle-mediated mild PTT can inhibit atherosclerotic progression,which provides new insights for developing safe and effective treatment methods for atherosclerosis.