ACS applied bio materials · 2025
M3-DPPE Liposomal Nanoparticles Encapsulating CLEC12A Enhance CD206-Mediated Endocytosis and Efficacy in the Collagen-Induced Arthritis Model.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Luo Shulin, Cai Junfeng, Yin Feng, Lu Laiya, Liu Zheng, Wang Yunxia, Fu Xiaocong, Ding Shuangfeng, Kojima Naoya, Ma Min
Аннотация
OBJECTIVE: This study aimed to investigate the efficacy of M3-DPPE liposomal nanoparticles encapsulated with mRNA encoding cytokines (M3-mRNAs) in targeting macrophages for the treatment of inflammation-induced joint injury.
METHODS: in vitro, M3-mRNAs were administered to peritoneal exudate macrophages (PEMs), and the uptake was assessed using flow cytometry. The mechanism of uptake was investigated by blocking the CLEC12A pathway with M3-SiCLEC12A and observing CD206-mediated endocytosis. In vivo, the distribution of Dir-labeled M3-drugs was monitored using IVIS imaging, and its accumulation in inflammatory and noninflammatory areas was evaluated. The therapeutic potential was evaluated in collagen-induced arthritis (CIA) model mice by assessing macrophage polarization, joint pathology, and cytokine expression.
RESULTS: in vitro studies demonstrated that M3-mRNAs were taken up significantly by PEMs via CD206-mediated endocytosis. In vivo imaging showed that Dir-labeled M3-drugs accumulated predominantly in inflammatory areas and subsequently in bone injury joints. Treatment with M3-drugs in collagen-induced arthritis model mice increased the population of F4/80+ and F4/80+/CD206+ M2 macrophages in inflamed joints, leading to reduced joint fibrosis and modulation of cytokine levels, including decreased pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, and INF-γ) and increased anti-inflammatory cytokines (IL-10 and TGF-β).
CONCLUSIONS: M3-SiCLEC12A enhanced CD206-mediated endocytosis of M3-mRNAs and M3-drugs in macrophages, promoting the production of corresponding proteins and modulating the immune microenvironment. This treatment approach shows promise in repairing inflammation-induced bone and joint injury by balancing pro-inflammatory and anti-inflammatory cytokines. However, further research is required to address drug tolerance and safety concerns and minimize potential side effects before clinical application in autoimmune diseases caused by inflammation.
METHODS: in vitro, M3-mRNAs were administered to peritoneal exudate macrophages (PEMs), and the uptake was assessed using flow cytometry. The mechanism of uptake was investigated by blocking the CLEC12A pathway with M3-SiCLEC12A and observing CD206-mediated endocytosis. In vivo, the distribution of Dir-labeled M3-drugs was monitored using IVIS imaging, and its accumulation in inflammatory and noninflammatory areas was evaluated. The therapeutic potential was evaluated in collagen-induced arthritis (CIA) model mice by assessing macrophage polarization, joint pathology, and cytokine expression.
RESULTS: in vitro studies demonstrated that M3-mRNAs were taken up significantly by PEMs via CD206-mediated endocytosis. In vivo imaging showed that Dir-labeled M3-drugs accumulated predominantly in inflammatory areas and subsequently in bone injury joints. Treatment with M3-drugs in collagen-induced arthritis model mice increased the population of F4/80+ and F4/80+/CD206+ M2 macrophages in inflamed joints, leading to reduced joint fibrosis and modulation of cytokine levels, including decreased pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, and INF-γ) and increased anti-inflammatory cytokines (IL-10 and TGF-β).
CONCLUSIONS: M3-SiCLEC12A enhanced CD206-mediated endocytosis of M3-mRNAs and M3-drugs in macrophages, promoting the production of corresponding proteins and modulating the immune microenvironment. This treatment approach shows promise in repairing inflammation-induced bone and joint injury by balancing pro-inflammatory and anti-inflammatory cytokines. However, further research is required to address drug tolerance and safety concerns and minimize potential side effects before clinical application in autoimmune diseases caused by inflammation.