Agomir-122-loaded nanoparticles coated with cell membrane of activated fibroblasts to treat frozen shoulder based on homologous targeting

• DOI: 10.1186/s12951-024-02403-w
• Publication Date: 2024-04-10T18:01:37Z
• Authors: Zhen Peng; Beijie Qi; Zhiwen Luo; Yaying Sun; Xingyu Zhang; Jinrong Lin; Jinhui Pang; Peng Zhang; Zhihu Zhao; Xianwen Wang; Jiwu Chen
• Keywords: Capsule; Internalization

As a common musculoskeletal disorder, frozen shoulder is characterized by thickened joint capsule and limited range of motion, affecting 2-5% the general population more than 20% patients with diabetes mellitus. Pathologically, fibrosis resulting from fibroblast activation key event. The activated fibroblasts are proliferative contractive, producing excessive collagen. Albeit high prevalence, effective anti-fibrosis modalities, especially fibroblast-targeting therapies, still lacking. In this study, microRNA-122 was first identified sequencing data as potential therapeutic agent to antagonize activation. Then, Agomir-122, an analog microRNA-122, loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Agomir-122@NP), carrier excellent biocompatibility for delivery. Moreover, relying on homologous targeting effect, we coated Agomir-122@NP cell membrane derived (Agomir-122@MNP), attempt inhibit proliferation, contraction, collagen production abnormally fibroblasts. After confirming effect Agomir-122@MNP in vitro, proved that effectively curtailed activation, ameliorated fibrosis, restored motion mouse models both prophylactically therapeutically. Overall, targeted delivery method developed promising translational value against shoulder.