Zhu Qicui, Chen Ruofei, Wu Xueting, Zhou Yuanyuan, Wang Zexin, Zhang Huaixuan, Zhu Haofang, Sun Lingyun, Shuai Zongwen
Department of Rheumatology and Immunology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Department of Rheumatology and Immunology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China.
Theranostics. 2025 May 30;15(13):6553-6571. doi: 10.7150/thno.108296. eCollection 2025.
Due to their anti-inflammatory and immunomodulatory capabilities, adipose-derived stem cells (ADSC) are currently considered a promising option for the management of rheumatoid arthritis (RA). To tackle the problems of immunogenicity and tumorigenicity linked to the direct use of cells, current research is focused on the development of effective nanomedicines utilizing ADSC-derived exosomes (ADSC-EXO) for cell-free regenerative medicine. Methotrexate (MTX) was loaded into mesoporous silica through physical adsorption to produce SiO-MTX, with subsequent incorporation into ADSC-EXO via ultrasonication to produce AE@SiO-MTX. Particle size, surface charge, and stability were characterized using dynamic light scattering (DLS) and zeta potential analysis. , the effects of the nanomaterials were evaluated by assessing the inverse polarization effect of AE@SiO-MTX on RAW264.7 macrophages, as well as on the migration and invasion capabilities of fibroblast-like synovial cells (FLS). targeting and therapeutic effects on joint inflammation were examined using adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) mouse models. The AE@SiO₂-MTX demonstrated sustained drug release, high biocompatibility, and rapid cellular internalization. , the delivery system alleviated chronic inflammation by inducing macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype, as well as suppressing FLS migration and invasion. studies revealed that administration of ADSC-EXO outperformed ADSC transplantation in alleviating RA symptoms. Intravenously delivered AE@SiO₂-MTX exhibited targeted accumulation in inflamed joints, significantly reducing joint swelling, synovial hyperplasia, and bone/cartilage degradation in CIA model mice. The findings show that AE@SiO₂-MTX is a robust cell-free therapeutic platform for RA management. Synergy between the immunomodulatory properties of ADSC-EXO and MTX controlled release, this system can overcome the limitations of conventional cell therapies and achieve targeted anti-inflammatory and tissue-protective effects. This strategy offers a promising translational avenue for RA treatment.
由于其抗炎和免疫调节能力，脂肪来源干细胞（ADSC）目前被认为是治疗类风湿性关节炎（RA）的一个有前景的选择。为了解决与直接使用细胞相关的免疫原性和致瘤性问题，当前的研究集中在开发利用ADSC衍生外泌体（ADSC-EXO）的有效纳米药物用于无细胞再生医学。通过物理吸附将甲氨蝶呤（MTX）负载到介孔二氧化硅中以制备SiO-MTX，随后通过超声处理将其掺入ADSC-EXO中以制备AE@SiO-MTX。使用动态光散射（DLS）和zeta电位分析对粒径、表面电荷和稳定性进行表征。此外，通过评估AE@SiO-MTX对RAW264.7巨噬细胞的反向极化作用以及对成纤维样滑膜细胞（FLS）的迁移和侵袭能力，来评估纳米材料的效果。使用佐剂诱导的关节炎（AIA）和胶原诱导的关节炎（CIA）小鼠模型检查对关节炎症的靶向和治疗效果。AE@SiO₂-MTX表现出持续的药物释放、高生物相容性和快速的细胞内化。此外，该递送系统通过诱导巨噬细胞从促炎M1表型向抗炎M2表型极化，以及抑制FLS迁移和侵袭来减轻慢性炎症。研究表明，给予ADSC-EXO在减轻RA症状方面优于ADSC移植。静脉内递送的AE@SiO₂-MTX在炎症关节中表现出靶向积累，显著减少CIA模型小鼠的关节肿胀、滑膜增生和骨/软骨降解。研究结果表明，AE@SiO₂-MTX是一种用于RA治疗的强大的无细胞治疗平台。ADSC-EXO的免疫调节特性与MTX控释之间的协同作用，该系统可以克服传统细胞疗法的局限性，并实现靶向抗炎和组织保护作用。该策略为RA治疗提供了一条有前景的转化途径。
