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

作　　者：Ting Dai Wenming He Shuangshuang Tu Jinru Han Bo Yuan Chenyang Yao Wenzhi Ren Aiguo Wu 

机构地区：[1]Department of Cardiology,The Affiliated Hospital of Medical School,Ningbo University,247 Renmin Road,Jiangbei District,Ningbo,Zhejiang Province,315020,China [2]Cixi Institute of Biomedical Engineering,International Cooperation Base of Biomedical Materials Technology and Application,CAS Key Laboratory of Magnetic Materials and Devices&Zhejiang Engineering Research Center for Biomedical Materials,Ningbo Institute of Materials Technology and Engineering,Chinese Academy of Sciences,1219 ZhongGuan West Road,Ningbo,315201,China [3]University of Chinese Academy of Sciences,No.1 Yanqihu East Road,Huairou District,Beijing,101408,China [4]Advanced Energy Science and Technology Guangdong Laboratory,Huizhou,516000,China

出　　处：《Bioactive Materials》2022年第11期18-28,共11页生物活性材料（英文）

基　　金：This work was supported by Natural Science Foundation of China(32171359,32025021,31971292);National Key R&D Program of China(2019YFA0405603,2018YFC0910601);Zhejiang Province Financial Supporting(LGF19C100001,2020C03110);Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province(No.2019E10020);Zhejiang Provincial Natural Science Foundation of China(LY20H020002);General research program of Zhejiang Provincial Department of health(WKJ-ZJ-2137);Key Scientific and Technological Special Project of Ningbo City(2020Z094);the Affiliated Hospital of Medical School of Ningbo University Youth Talent Cultivation Program(FYQM-KY-202002);Furthermore,the authors also acknowledge National Synchrotron Radiation Laboratory in Hefei for High End User Cultivation Fund(2020HSC-UE006);Shanghai Syn-chrotron Radiation Facility at Line BL15U for X-ray fluorescence imaging.

摘　　要：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.

关 键 词：Atherosclerosis Black TiO_(2)nanoparticles PHOTOTHERAPY Cholesterol homeostasis 

分 类 号：R318[医药卫生—生物医学工程] R54[医药卫生—基础医学]