Apoptotic Neutrophil Membrane-Camouflaged Liposomes for Dually Targeting Synovial Macrophages and Fibroblasts to Attenuate Osteoarthritis

作者：Deng, Caifeng; Chen, Yuxiao; Zhao, Xuan; Yu, Liukang; Xiao, Yongbing; Li, Hui; Zhang, Yuqing; Ai, Kelong; Zhou, Dongfang; Bai, Xiaochun; Gong, Tao; Wei, Jie^*; Zeng, Chao^*; Lei, Guanghua^*

来源：ACS applied materials & interfaces, 2023.

DOI：10.1021/acsami.3c05861

• apoptotic neutrophil membrane-camouflaged liposome
• M1 macrophages
• synovial fibroblasts
• dually targeting
• extended joint retention

No current pharmacological approach is capable of simultaneouslyinhibiting the symptomatology and structural progression of osteoarthritis.M1 macrophages and activated synovial fibroblasts (SFs) mutually contributeto the propagation of joint pain and cartilage destruction in osteoarthritis.Here, we report the engineering of an apoptotic neutrophil membrane-camouflagedliposome (termed "NM@Lip") for precise delivery of triamcinoloneacetonide (TA) by dually targeting M1 macrophages and activated SFsin osteoarthritic joints. NM@Lip has a high cellular uptake in M1macrophages and activated SFs. Furthermore, TA-loaded NM@Lip (TA-NM@Lip)effectively repolarizes M1 macrophages to the M2 phenotype and transformspathological SFs to the deactivated phenotype by inhibiting the PI3K/Aktpathway. NM@Lip retains in the joint for up to 28 days and selectivelydistributes into M1 macrophages and activated SFs in synovium withlow distribution in cartilage. TA-NM@Lip decreases the levels of pro-inflammatorycytokines, chemokines, and cartilage-degrading enzymes in osteoarthriticjoints. In a rodent model of osteoarthritis-related pain, a singleintra-articular TA-NM@Lip injection attenuates synovitis effectivelyand achieves complete pain relief with long-lasting effects. In arodent model of osteoarthritis-related joint degeneration, repeatedintra-articular TA-NM@Lip injections induce no obvious cartilage damageand effectively attenuate cartilage degeneration. Taken together,TA-NM@Lip represents a promising nanotherapeutic approach for osteoarthritistherapy.

• 单位
  四川大学; 南方医科大学