机构：[1]Department of Pharmacy, Deyang People's Hospital, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, China.[2]Sichuan Clinical Medical Research Center for Neurological Diseases, Deyang People's Hospital, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, China.[3]Operating Room, Deyang People's Hospital, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, China.[4]Department of Scientific & Education, Deyang People's Hospital, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, PR China.[5]Department of Neurosurgery, Deyang People's Hospital, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, PR China.[6]Centre for Translational Research in Cancer, Sichuan Cancer Hospital & Institute, Chengdu, China.四川省肿瘤医院[7]School of Medicine, University of Electronic Science and Technology, Chengdu, China.[11] School of Medicine, University of Electronic Science and Technology, Chengdu 610000, China
Rheumatoid arthritis (RA) is a chronic autoimmune inflammation. Excessive proliferation and inadequate apoptosis of synovial macrophages are the crucial events of RA. Therefore, delivering therapeutic molecules to synovial macrophages specifically to tackle apoptotic insufficiency probably can be an efficient way to reduce joint inflammation and bone erosion. Based on the characteristics of dextran sulphate (DS) specifically binding scavenger receptor A (SR-A) on macrophage and celastrol (CLT) inducing apoptosis, we designed synovial macrophage-targeted nano-emulsions encapsulated with CLT (SR-CLTNEs) and explored their anti-RA effect. After intravenous injection, fluorescence-labelled SR-CLTNEs successfully targeted inflammatory joints and synovial macrophages in a mouse model of RA, with the macrophage targeting efficiency of SR-CLTNEs, CLTNEs and free DID was 20.53%, 13.93% and 9.8%, respectively. In vivo and in vitro studies showed that SR-CLTNEs effectively promoted the apoptosis of macrophages, reshaped the balance between apoptosis and proliferation, and ultimately treated RA in a high efficiency and low toxicity manner. Overall, our work demonstrates the efficacy of using SR-CLTNEs as a novel nanotherapeutic approach for RA therapy and the great translational potential of SR-CLTNEs.
基金：
This work was supported by the National Natural Science
Foundation of China [32301192, 82300276], the Key Research and
Development Project of Deyang Science and Technology Bureau
[2023SZZ002], the Sichuan Medical Research Youth Innovation
Project [Q22026] and the National Incubation Project of Deyang
People’s Hospital [FHG202302]
第一作者机构：[1]Department of Pharmacy, Deyang People's Hospital, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, China.[2]Sichuan Clinical Medical Research Center for Neurological Diseases, Deyang People's Hospital, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, China.[*1]Department of Pharmacy, Deyang People’s Hospital, Affiliated Hospital of Chengdu University of traditional Chinese Medicine, Deyang 618000, China , Sichuan Clinical Medical Research Center for Neurological Diseases, Deyang People’s Hospital, Affiliated Hospital of Chengdu University of traditional Chinese Medicine, Deyang 618000, China
通讯作者：
通讯机构：[1]Department of Pharmacy, Deyang People's Hospital, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, China.[2]Sichuan Clinical Medical Research Center for Neurological Diseases, Deyang People's Hospital, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, China.[5]Department of Neurosurgery, Deyang People's Hospital, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Deyang, PR China.[6]Centre for Translational Research in Cancer, Sichuan Cancer Hospital & Institute, Chengdu, China.[7]School of Medicine, University of Electronic Science and Technology, Chengdu, China.[*1]Department of Pharmacy, Deyang People’s Hospital, Affiliated Hospital of Chengdu University of traditional Chinese Medicine, Deyang 618000, China , Sichuan Clinical Medical Research Center for Neurological Diseases, Deyang People’s Hospital, Affiliated Hospital of Chengdu University of traditional Chinese Medicine, Deyang 618000, China[*2]Department of Neurosurgery, Deyang People’s Hospital, Affiliated Hospital of Chengdu University of traditional Chinese Medicine, Deyang 618000, PR China, Sichuan Clinical Medical Research Center for Neurological Diseases, Deyang People’s Hospital, Affiliated Hospital of Chengdu University of traditional Chinese Medicine, Deyang 618000, China[*3]Centre for Translational Research in Cancer, Sichuan Cancer Hospital & Institute, Chengdu 610000, China
推荐引用方式(GB/T 7714)：
Li Chenglong,Li Yan,Zeng Qing,et al.Celastrol nano-emulsions selectively regulate apoptosis of synovial macrophage for alleviating rheumatoid arthritis[J].JOURNAL OF DRUG TARGETING.2024,32(6):724-735.doi:10.1080/1061186X.2024.2352757.
APA：
Li Chenglong,Li Yan,Zeng Qing,Zhou Yang,Su Huaiyu...&Li Chen.(2024).Celastrol nano-emulsions selectively regulate apoptosis of synovial macrophage for alleviating rheumatoid arthritis.JOURNAL OF DRUG TARGETING,32,(6)
MLA：
Li Chenglong,et al."Celastrol nano-emulsions selectively regulate apoptosis of synovial macrophage for alleviating rheumatoid arthritis".JOURNAL OF DRUG TARGETING 32..6(2024):724-735
