Cholesterol modulates the physiological response to nanoparticles by changing the composition of protein corona

Tang, Huan1,2; Zhang, Ying1,2; Yang, Tong1,2; Wang, Chen1,2; Zhu, Yinhua1,2; Qiu, Liangjia1,2; Liu, Jiahui3; Song, Yang1,2; Zhou, Lirue1,2; Zhang, Junzhe1,2; Wong, Yin Kwan4; Liu, Yuanfang3,5; Xu, Chengchao1,2,6,7; Wang, Haifang2,5; Wang, Jigang1,2,6,7,8,9

2023-09-01

10.1038/s41565-023-01455-7

NATURE NANOTECHNOLOGY   影响因子和分区

1748-3387

1748-3395

["Here the authors report that the metabolome profile is an unexploited factor impacting the targeting efficacy and safety of nanomedicines, using cholesterol as an example, showing a way and need to develop personalized nanomedicines by harnessing disease-related metabolites.","Nanoparticles (NPs) in biological fluids form a layer of biomolecules known as the protein corona. The protein corona has been shown to determine the biological identity and in vivo fate of NPs, but whether and how metabolites, especially disease-related small molecules, regulate the protein corona and subsequently impact NP fate in vivo is relatively poorly understood. Here we report on the effects of cholesterol on the generation of protein corona and subsequent effects. We find that high levels of cholesterol, as in hypercholesterolemia, result in a protein corona with enriched apolipoproteins and reduced complement proteins by altering the binding affinity of the proteins to the NPs. The cholesterol-mediated protein corona can induce stronger inflammatory responses to NPs in macrophages and promote the cellular uptake of NPs in hepatocytes by enhancing the recognition of lipoprotein receptors when compared with normal protein corona. The result of in vivo biodistribution assays shows that, compared with healthy mice, NPs in hypercholesterolemic mice were more likely to be delivered to the liver, spleen and brain, and less likely to be delivered to the lungs. Our findings reveal that the metabolome profile is an unexploited factor impacting the target efficacy and safety of nanomedicines, providing a way to develop personalized nanomedicines by harnessing disease-related metabolites."]

SCI ; EI

英语

NI论文

通讯

National Key Research and Development Program of China["2020YFA0908000","2022YFC2303600"] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[ZYYCXTD-C-202002] ; National Natural Science Foundation of China["32201177","32000026","82141001","82274182","82074098"] ; CACMS Innovation Fund["CI2021A05101","CI2021A05104"] ; Scientific and Technological Innovation Project of China Academy of Chinese Medical Sciences[CI2021B014] ; Science and Technology Foundation of Shenzhen[JCYJ20210324115800001] ; National Key Ramp;D Program of China Key projects for international cooperation on science, technology and innovation[2020YFE0205100] ; Fundamental Research Funds for the Central Public Welfare Research Institutes["ZZ14-YQ-061","ZZ16-ND-1024","ZZ14-YQ-057","ZZ14-YQ-050","ZZ14-YQ-051","ZZ14-FL-002","ZZ14-ND-010","ZZ15-ND-10"] ; GuangDong Basic and Applied Basic Research Foundation[2021A1515012164] ; Shenzhen Key Laboratory of Kidney Diseases[ZDSYS201504301616234] ; Shenzhen Governmental Sustainable Development Fund[KCXFZ20201221173612034]

Science & Technology - Other Topics ; Materials Science

Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:001042115200003

NATURE PORTFOLIO

20233814744268

Binding energy ; Cholesterol ; Lipoproteins ; Mammals ; Metabolism ; Metabolites ; Physiological models ; Safety factor

Biological Materials and Tissue Engineering:461.2 ; Nanotechnology:761 ; Physical Chemistry:801.4 ; Organic Compounds:804.1 ; Accidents and Accident Prevention:914.1 ; Solid State Physics:933

Web of Science

1.China Acad Chinese Med Sci, State Key Lab Qual Ensurance & Sustainable Use Dao, Artemisinin Res Ctr, Beijing, Peoples R China
2.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing, Peoples R China
3.Peking Univ, Coll Chem & Mol Engn, Beijing Natl Lab Mol Sci, Beijing, Peoples R China
4.Natl Univ Singapore, Dept Biol Sci, Singapore, Singapore
5.Shanghai Univ, Inst Nanochem & Nanobiol, Shanghai, Peoples R China
6.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Dept Nephrol,Shenzhen Key Lab Kidney Dis, Shenzhen, Peoples R China
7.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Shenzhen Clin Res Ctr Geriatr, Shenzhen, Peoples R China
8.Southern Med Univ, Sch Pharmaceut Sci, Guangdong Prov Key Lab New Drug Screening, Guangzhou, Peoples R China
9.Southern Med Univ, Sch Tradit Chinese Med, Guangzhou, Peoples R China

Tang, Huan,Zhang, Ying,Yang, Tong,et al. Cholesterol modulates the physiological response to nanoparticles by changing the composition of protein corona[J]. NATURE NANOTECHNOLOGY,2023,18(9):1067-1077.

Tang, Huan.,Zhang, Ying.,Yang, Tong.,Wang, Chen.,Zhu, Yinhua.,...&Wang, Jigang.(2023).Cholesterol modulates the physiological response to nanoparticles by changing the composition of protein corona.NATURE NANOTECHNOLOGY,18(9),1067-1077.

Tang, Huan,et al."Cholesterol modulates the physiological response to nanoparticles by changing the composition of protein corona".NATURE NANOTECHNOLOGY 18.9(2023):1067-1077.