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Fe3O4与SiO2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-PEG-CD纳米颗粒较好的体内相容性。
Abstract
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 Fe3O4 and SiO2. 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 to β-CD, PEG/β-CD and polypseudorotaxanes will limit the intramuscular diffusion of nanoparticles, resulting in prolonged intramuscular residence time of CDMNP and CDMNP-PEG-CD, 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.
关键词
磁纳米颗粒； CDMNP-PEG-CD； SOMNP； CDMNP； 免疫反应； 骨骼肌
Key words
Magnetic nanoparticles; CDMNP-PEG-CD; SOMNP; CDMNP; Immune response /
Skeletal muscle
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参考文献
[1] Cortajarena AL, Ortega D, Ocampo SM, et al. Engineering Iron Oxide Nanoparticles for Clinical Settings[J]. Nanobiomedicine (Rij), 2014, 1:2. DOI: 10.5772/58841.
[2] Nel AE, Madler L, Velegol D, et al. Understanding biophysicochemical interactions at the nano-bio interface[J]. Nat Mater, 2009, 8(7):543-557. DOI: 10.1038/nmat2442
[3] Sakulkhu U, Mahmoudi M, Maurizi L, et al. Significance of surface charge and shell material of superparamagnetic iron oxide nanoparticle (SPION) based core/shell nanoparticles on the composition of the protein corona[J]. Biomater Sci, 2015, 3(2):265-278. DOI: 10.1039/c4bm00264d.
[4] Maboudi SA, Shojaosadati SA, Arpanaei A. Synthesis and characterization of multilayered nanobiohybrid magnetic particles for biomedical applications[J]. Materials & Design, 2017,115:317-324. DOI：10.1016/j.matdes.2016.11.064.
[5] Ke Y, Zhang X, Liu C, et al. Polypseudorotaxane functionalized magnetic nanoparticles as a dual responsive carrier for roxithromycin delivery[J]. Mater Sci Eng C Mater Biol Appl, 2019, 99:159-170. DOI: 10.1016/j.msec.2019.01.078.
[6] Yun YH, Lee BK, Park K. Controlled Drug Delivery: Historical perspective for the next generation[J]. J Control Release, 2015, 219: 2-7. DOI: 10.1016/j.jconrel.2015.10.005.
[7] Romera SA, Hilgers LA, Puntel M, et al. Adjuvant effects of sulfolipo-cyclodextrin in a squalane-in-water and water-in-mineral oil emulsions for BHV-1 vaccines in cattle.[J]. Vaccine, 2000, 19(1):132-141. DOI: 10.1016/s0264-410x(00)00104-3.
[8] Wu C, Xiang X, Yue Y, et al. CpG-PEG Conjugates and their immune modulating effects after systemic administration[J]. Pharmaceutical Research, 2018, 35(4): 80. DOI: 10.1007/s11095-018-2355-z.
[9] Yang Q, Lai S K. Anti-PEG immunity: emergence, characteristics, and unaddressed questions[J]. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2015, 7(5): 655-677. DOI: 10.1002/wnan.1339.
[10] Tidball JG. Inflammatory processes in muscle injury and repair[J]. Am J Physiol Regul Integr Comp Physiol, 2005, 288(2):R345. DOI: 10.1152/ajpregu.00454.2004.
[11] Arnold L, Henry A, Poron F, et al. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis[J]. J Exp Med, 2007, 204(5):1057-1069. DOI: 10.1084/jem.20070075.
[12] Chenthamara D, Subramaniam S, Ramakrishnan SG, et al. Therapeutic efficacy of nanoparticles and routes of administration[J]. Biomater Res, 2019, 23:20. DOI: 10.1186/s40824-019-0166-x.
[13] Takeuchi I, Nobata S, Oiri N, et al. Biodistribution and excretion of colloidal gold nanoparticles after intravenous injection: Effects of particle size[J]. Biomed Mater Eng, 2017, 28(3):315-323. DOI: 10.3233/BME-171677.
[14] Xie P, Yang S T, He T, et al. Bioaccumulation and toxicity of carbon nanoparticles suspension injection in intravenously exposed mice[J]. Int J Mol Sci, 2017, 18(12):2563. DOI: 10.3390/ijms18122562.
[15] Frank JA, Zywicke H, Jordan EK, et al. Magnetic intracellular labeling of mammalian cells by combining (FDA-approved) superparamagnetic iron oxide MR contrast agents and commonly used transfection agents[J]. Acad Radiol, 2002, 9（Suppl 2）:S484-S487. DOI: 10.1016/s1076-6332(03)80271-4.
[16] Brigitte M, Schilte C, Plonquet A, et al. Muscle resident macrophages control the immune cell reaction in a mouse model of notexin-induced myoinjury[J]. Arthritis Rheum, 2010, 62(1):268-279. DOI: 10.1002/art.27183.
[17] Page G, Chevrel G, Miossec P. Anatomic localization of immature and mature dendritic cell subsets in dermatomyositis and polymyositis: Interaction with chemokines and Th1 cytokine-producing cells[J]. Arthritis Rheum, 2004, 50(1):199~208. DOI: 10.1002/art.11428.
[18] Jimenez-Perianez A, Abos GB, Lopez RJ, et al. Mesoporous silicon microparticles enhance MHC class I cross-antigen presentation by human dendritic cells[J]. Clin Dev Immunol, 2013, 2013:362163. DOI: 10.1155/2013/362163.
基金
国家自然科学基金面上项目（32071181）；广东省自然科学基金面上项目（2019A1515011305）；广州市科技计划项目（202002030497）
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