超声协同基于外泌体的IL-10@exosome-iRGD靶向生物纳米囊泡促巨噬细胞M2极化治疗关节炎的实验研究

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中文摘要
类风湿关节炎及骨关节炎是致残的重要病因,促进巨噬细胞M1型向M2型转化,有助于炎症消退及组织修复。IL-10能促进巨噬细胞M2极化,该途径已逐渐成为治疗关节炎的新策略之一。以往研究运用多种药物载体,如脂质体、聚合物囊泡等,以降低药物的副作用和提高有效性,但载药率低、稳定性差以及高免疫原性等不足限制了其应用。而活细胞分泌的外泌体(exosome)因具有良好的生物相容性、高生物渗透性、低免疫原性和低毒性等优点,有望成为药物的新型高效运输载体。但如何实现外泌体在病变区的靶向聚集是需要解决的关键问题。基于我们前期研究证实超声联合微泡可促进载药脂质体对炎性滑膜的靶向释药,我们拟通过树突状细胞分泌的外泌体制备靶向生物纳米囊泡IL-10@exosome-iRGD,利用超声联合微泡实现外泌体在关节靶向浓聚,促进巨噬细胞M2极化,探讨机理并评估疗效,旨在为探索关节炎新型、高效的治疗方法提供理论与实验依据。
英文摘要
Rheumatoid arthritis and osteoarthritis are important causes of disability. Promoting the polarizationof macrophages from M1 type to M2 type can help inflammation subside and tissue repair. IL-10 can promote the M2 polarization of macrophages, which has gradually become one of the new strategies for the treatment of arthritis. In previous studies, multiple drug carriers, such as liposomes and polymer vesicles, were used to reduce side effects and improve effectiveness of drugs, but their applications were limited by low drug loading rate, poor stability and high immunogenicity. It is expected that the exosome secreted by living cells will be a new effective drug delivery vehicle due to its excellent biocompatibility, high biopermeability, low immunogenicity and low toxicity. However, how to achieve the targeted aggregation of exosomes in the lesion area is a key problem thatneededto be solved. Based on our previous study which confirmed that the ultrasound-mediated microbubbledestructioncould promote targeting drug releaseto inflammatory synovitisofdrug-loaded liposome, we proposed topreparetargeted biological nanometer vesicles IL-10@exosome-iRGD basedonexosomessecretedbydendritic cells, to use ultrasound combined with microbubbles to achieve the joint targeted exosome concentration,to promote the M2 macrophage polarization, to explore the mechanism and evaluate the efficacy.The aim of this study is to provide theoretical and experimental basis for the exploration of new and efficient methods of autotherapy for arthritis.
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DOI:10.1186/s12951-021-00835-2
发表时间:2021-03-31
期刊:Journal of nanobiotechnology
影响因子:10.2
作者:Xiang X;Pang H;Ma T;Du F;Li L;Huang J;Ma L;Qiu L
通讯作者:Qiu L
DOI:10.1016/j.cclet.2020.12.004
发表时间:2021-05-04
期刊:CHINESE CHEMICAL LETTERS
影响因子:9.1
作者:Liu, Hui;Xiang, Xi;Qiu, Li
通讯作者:Qiu, Li
DOI:10.1039/d2tb01219g
发表时间:2022
期刊:Journal of Materials Chemistry B
影响因子:7
作者:Yuanjiao Tang;Zihe Wu;Ruiqian Guo;Jianbo Huang;Xiao Rong;Bihui Zhu;Liyun Wang;Lang Ma;Chong Cheng;Li Qiu
通讯作者:Li Qiu
DOI:10.1002/adfm.202007475
发表时间:2020-11-02
期刊:ADVANCED FUNCTIONAL MATERIALS
影响因子:19
作者:Tang, Qing;Cao, Sujiao;Cheng, Chong
通讯作者:Cheng, Chong
DOI:10.1002/adma.202003065
发表时间:2020-10-30
期刊:ADVANCED MATERIALS
影响因子:29.4
作者:Ma, Lang;Jiang, Fuben;Qiu, Li
通讯作者:Qiu, Li
超声联合载Ru-Por杂化膜囊泡多模式协同治疗黑色素瘤的实验研究
- 批准号:--
- 项目类别:面上项目
- 资助金额:53万元
- 批准年份:2022
- 负责人:邱逦
- 依托单位:
超声联合微泡介导载药声敏eLiposomes对炎性关节病靶向治疗的实验研究
- 批准号:81671696
- 项目类别:面上项目
- 资助金额:58.0万元
- 批准年份:2016
- 负责人:邱逦
- 依托单位:
超声靶向破坏微泡不同途径转染生长因子pDNA及siRNA促损伤肌腱再生及抑制粘连的实验研究
- 批准号:81271585
- 项目类别:面上项目
- 资助金额:65.0万元
- 批准年份:2012
- 负责人:邱逦
- 依托单位:
超声空化效应损伤类风湿性关节炎滑膜血管翳的机理研究
- 批准号:30801067
- 项目类别:青年科学基金项目
- 资助金额:20.0万元
- 批准年份:2008
- 负责人:邱逦
- 依托单位:
国内基金
海外基金
