Existing therapeutics for autoimmune diseases remain problematic due to low efficacy, severe side effects, and difficulties to reach target tissues. Herein, we design multifunctional fusion nanovesicles that can target lesions for the treatment of autoimmune skin diseases. The grapefruit-derived exosome-like nanovesicles (GEVs) with anti-inflammatory and antioxidant effects are first encapsulated with CX5461, an immunosuppressant with anti-proliferative properties to form GEV@CX5461. In order to enhance therapeutic efficiency and safety, GEV@CX5461 are then fused with CCR6+ nanovesicles derived from membranes of engineered gingiva-derived mesenchymal stem cells (GMSCs). The resulting FV@CX5461 not only maintain the bioactivity of GEVs, CX5461, and GMSC membranes but also home to inflamed tissues rich in chemokine CCL20 through the chemotaxis function of CCR6 on FVs. Moreover, FV@CX5461 reduce the secretion of inflammatory factors, calm down Th17 cell activation, and induce Treg cell infiltration. Finally, impressive therapeutic efficiency in both psoriasis and atopic dermatitis disease models is demonstrated using FV@CX5461 to reshape the unbalanced immune microenvironment. A nanotherapeutic drug delivery strategy is developed using fusion nanovesicles derived from plant and animal cells with high clinical potential.

中文翻译：

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植物外泌体与工程间充质干细胞衍生的纳米囊泡融合，用于自身免疫性皮肤病的协同治疗

由于疗效低、副作用严重且难以到达靶组织，现有的自身免疫性疾病治疗方法仍然存在问题。在这里，我们设计了多功能融合纳米囊泡，可以靶向病变来治疗自身免疫性皮肤病。首先将具有抗炎和抗氧化作用的葡萄柚来源的外泌体样纳米囊泡（GEV）封装在具有抗增殖特性的免疫抑制剂CX5461中，形成GEV@CX5461。为了提高治疗效率和安全性，GEV@CX5461 随后与源自工程牙龈源性间充质干细胞 (GMSC) 膜的 CCR6+ 纳米囊泡融合。由此产生的FV@CX5461不仅维持了GEV、CX5461和GMSC膜的生物活性，而且还通过CCR6对FV的趋化功能，使富含趋化因子CCL20的发炎组织归巢。此外，FV@CX5461还可以减少炎症因子的分泌，平息Th17细胞的活化，并诱导Treg细胞浸润。最后，使用 FV@CX5461 重塑不平衡的免疫微环境在银屑病和特应性皮炎疾病模型中显示出令人印象深刻的治疗效果。使用源自植物和动物细胞的融合纳米囊泡开发了一种纳米治疗药物递送策略，具有很高的临床潜力。