{
  "abstract": "Background The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly increasing with high risk to develop cirrhosis, hepatocellular carcinoma (HCC) and other end-stage liver diseases. However, only two drugs, resmetirom and semaglutide, have been approved by the US food and drug administration (FDA) for the treatment of MASLD, with relative low efficient and obvious side effects. Nanomaterials emerged with constantly growing availability of disease therapy benefiting from their well biocompatibility and appropriate properties.Objective The aim of our present study is to identify and fabricate new nanoparticles with high clinical translational potential for MASLD therapy.Design We systematically screened biocompatible nanoparticles for anti-MASLD capacities in vitro by evaluating their regulatory effects on perilipin-2 (PLIN2), the key molecule in lipid droplet (LD) formation and stability. The exact effects and molecular mechanisms of the identified nanoparticle on MASLD were explored in both cellular and animal models.Results We identified a carboxyl fullerene derivative, named four malonate groups-substituted C 70 fullerene (QF70), as the most potent candidate for MASLD therapy. Notably, QF70 could facilitate lysosomal degradation of PLIN2. More importantly, oral administration of QF70 robustly blocked both diet-induced and leptin deficiency-induced MASLD development with significant improvement in obesity and insulin resistance. We further validated the clinical application potential of QF70 in MASLD-related metabolic disorders in a non-primate model.Conclusions This study provides proof-of-concept supporting a nanoparticle-based agent as a LD homeostasis-targeted therapeutic to treat MASLD and related metabolic diseases.",
  "authors": [
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China",
        "Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China"
      ],
      "name": "Toujun Zou"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China",
        "Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Juan Wan"
    },
    {
      "affiliations": [
        "Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, China"
      ],
      "name": "Rufang Liao"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China",
        "Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Lan Bai"
    },
    {
      "affiliations": [
        "School of Basic Medical Sciences, Wuhan University, Wuhan, China"
      ],
      "name": "Xinyan Li"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China",
        "Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Xu Cheng"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China",
        "Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Junjie Zhou"
    },
    {
      "affiliations": [
        "School of Basic Medical Sciences, Wuhan University, Wuhan, China"
      ],
      "name": "Qinchao Tang"
    },
    {
      "affiliations": [
        "School of Basic Medical Sciences, Wuhan University, Wuhan, China"
      ],
      "name": "Yufeng Zhang"
    },
    {
      "affiliations": [
        "College of Pharmacy, Guizhou Medical University, Guiyang, China"
      ],
      "name": "Chong Zhao"
    },
    {
      "affiliations": [
        "Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China"
      ],
      "name": "Weiyi Qu"
    },
    {
      "affiliations": [
        "School of Basic Medical Sciences, Wuhan University, Wuhan, China"
      ],
      "name": "Jinjie Yang"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Xiang Zhang"
    },
    {
      "affiliations": [
        "Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Tian Tian"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China",
        "Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Xinxin Yao"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Zhiwei Cai"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China",
        "School of Basic Medical Sciences, Wuhan University, Wuhan, China"
      ],
      "name": "Song Tian"
    },
    {
      "affiliations": [
        "Jiangsu Key Lab of Drug Screening, China Pharmaceutical University, Nanjing, China"
      ],
      "name": "Jingwei Jiang"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China",
        "Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Yufeng Hu"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China",
        "Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Hailong Yang"
    },
    {
      "affiliations": [
        "Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China"
      ],
      "name": "Ejuan Zhang"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Yun Chen"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Bingqiong Yu"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China",
        "Clinical Research Center, Central South University Third Xiangya Hospital Xiangya International Medical Center, Changsha, Hunan, China"
      ],
      "name": "Jingjing Cai"
    },
    {
      "affiliations": [
        "Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, China"
      ],
      "name": "Haibo Xu"
    },
    {
      "affiliations": [
        "CAS Research/Education Center for Excellence in Molecular Sciences, Chinese Academy of Sciences, Beijing, China"
      ],
      "name": "Chunru Wang"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China"
      ],
      "name": "Xiao-Jing Zhang"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China",
        "Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China"
      ],
      "name": "Zhi- Gang She"
    },
    {
      "affiliations": [
        "State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute",
        "School of Pharmacy",
        "First Affiliated Hospital, Gannan Medical University, Ganzhou, China",
        "Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China",
        "Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, China"
      ],
      "name": "Hongliang Li"
    }
  ],
  "title": "Discovery of a carboxyl fullerene derivative as a new lipid droplet regulator inhibiting MASLD",
  "uid": "23320006-d5d2-5270-b0cc-a4252baa55fb"
}