CDMNP-PEG-CD磁纳米颗粒诱导的骨骼肌反应性分析

Analysis of skeletal muscle reactivity induced by CDMNP-PEG-CD magnetic nanoparticles

目的探讨SOMNP、CDMNP及CDMNP-PEG-CD磁性纳米颗粒置入小鼠骨骼肌所诱发的免疫反应性。方法以磁性Fe;O;与SiO;复合制备SOMNP,将聚乙二醇(PEG)、环糊精(β-CD)分子链接SOMNP合成CDMNP,进一步添加聚假单胞烷(polypseudorotaxanes)合成CDMNP-PEG-CD磁性纳米颗粒。分别将3种纳米颗粒置入B6小鼠腓肠肌。组化染色、免疫荧光及FACS分析,分别评估不同置入时段SOMNP、CDMNP和CDMNP-PEG-CD纳米颗粒所诱发的肌毒性及肌内炎性渗出特征。结果SOMNP链接β-CD、PEG/β-CD及polypseudorotaxanes将限制纳米颗粒的肌内扩散,导致CDMNP和CDMNP-PEG-CD在肌内的滞留时间延长、材料邻近区肌细胞坏死、肌内单核/巨噬细胞聚集。较之CDMNP-PEG-CD,CDMNP纳米颗粒吸引更多T细胞进入肌组织。结论SOMNP、CDMNP及CDMNP-PEG-CD纳米颗粒均为潜在的体内免疫诱导物。polypseudorotaxanes修饰赋予CDMNP-PEGCD纳米颗粒较好的体内相容性。

Objective To investigate the immunoreactivity induced by SOMNP,CDMNP and CDMNP-PEG-CD magnetic nanoparticles implanted into mouse skeletal muscle.Methods SOMNP was prepared by compounding magnetic Fe;O;and SiO;.Polyethylene glycol(PEG)and cyclodextrin(β-CD)molecules were linked to SOMNP to synthesize CDMNP,and polypseudorotaxanes were further added to synthesize CDMNP-PEG-CD magnetic nanoparticles.particles.Three kinds of nanoparticles were placed into the gastrocnemius muscle of B6 mice,respectively.Histochemical staining,immunofluorescence and FACS analysis were used to evaluate the characteristics of myotoxicity and intramuscular inflammatory exudation induced by SOMNP,CDMNP and CDMNP-PEG-CD nanoparticles at different implantation periods.Results Linking of SOMNP toβ-CD,PEG/β-CD and polypseudorotaxanes will limit the intramuscular diffusion of nanoparticles,resulting in prolonged intramuscular residence time of CDMNP and CDMNP-PEGCD,myocyte necrosis in the vicinity of the material,intramuscular mononuclear/Macrophage aggregation.Compared with CDMNP-PEG-CD,CDMNP nanoparticles attracted more T cells into muscle tissue.Conclusion SOMNP,CDMNP and CDMNP-PEG-CD nanoparticles are all potential immune inducers in vivo.The modification of polypseudorotaxanes endowed CDMNP-PEG-CD nanoparticles with better in vivo compatibility.