Treatment of hemophilic arthropathy by immunomodulatory extracellular vesicle delivered by liposome hybrid nanoparticles  

作　　者：Dong Wang Wenzhe Chen Jiali Chen Du He Yanli Pan Pinger Wang Qinghe Zeng Mancang Gu Peijian Tong Di Chen Hongting Jin 

机构地区：[1]Institute of Orthopaedics and Traumatology,The First Affliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine),Department of Orthopedic Surgery,Hangzhou Hospital of Traditional Chinese Medicine,Zhejiang Chinese Medical University,Hangzhou,China [2]The College of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou,China [3]Department of Orthopaedic Surgery,The First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou,China [4]Faculty of Pharmaceutical Sciences,Shenzhen Institute of Advanced Technology,Shenzhen,China

出　　处：《Bioactive Materials》2024年第10期47-63,共17页生物活性材料（英文）

基　　金：supported by the Zhejiang Provincial Natural Science Foundation of China(LR23H270001 and LQ22H270006);National Natural Science Foundation of China(82274280 and 82305005).

摘　　要：In individuals afflicted with hemophilia,characterized by a deficiency of coagulation factor VIII(FVIII),the occurrence of spontaneous recurrent intra-articular hemorrhage precipitates the emergence of hemophilic arthropathy(HA).Although clotting factor replacement therapy reduces joint bleeding clinically,clotting factors need to be injected frequently due to the rapid diffusion of the drug.Hence,a novel drug delivery approach may be developed to improve the drug therapy.Platelet-derived extracellular vesicles(PEVs)are known to possess anti-inflammatory and hemostatic properties and could be used as a potential HA therapy.In this study,we constructed a PEV-LS@FVIII nanotherapeutic system by combining thioketal(TK),liposomes(LS),and FVIII to form the LS@FVIII complexes,and then hybridizing PEV with [e-mail] results demonstrated that PEVLS@FVIII could efficiently facilitate FVIII delivery and specifically target the injured knee joint.Both in vitro and in vivo studies showed a reduction in the M1 phenotype of macrophages and an enhancement of the M2 phenotype,compared to FVIII free control.Furthermore,PEV-LS@FVIII appeared to alleviate HA-induced cartilage damage.In conclusion,our findings demonstrate that PEV-LS@FVIII could delay the progression of HA by targeting bleeding joints,modulating macrophage polarization to suppress inflammation,and mitigating cartilage damage.

关 键 词：Hemophilic arthropathy Extracellular vesicles Recombinant factor VIII IMMUNOMODULATION CARTILAGE 

分 类 号：R554.1[医药卫生—血液循环系统疾病]