Targeting Macrophages and Synoviocytes Intracellular Milieu to Augment Anti-Inflammatory Drug Potency
Targeting Macrophages and Synoviocytes Intracellular Milieu to Augment Anti-Inflammatory Drug Potency
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DOI：
10.1002/adtp.202100167
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发表时间：
2022-01-10
影响因子：
4.6
通讯作者：
Battaglia, Giuseppe
中科院分区：
文献类型：
--
作者：
Gouveia, Virginia M.;Rizzello, Loris;Battaglia, Giuseppe
使用关节炎的临床前体内模型和缓解疾病的金标准抗风湿药物甲氨蝶呤、pH 响应性磷酸胆碱聚合物囊泡，可产生抗炎和抗关节炎治疗功效，同时大大减少脱靶毒性。首先，聚合物囊泡在发炎关节的滑膜内选择性积累。其次，聚合物囊泡通过清道夫受体靶向活化的巨噬细胞和滑膜细胞，允许它们通过内吞作用被摄取。第三，聚合物囊泡的 pH 响应性使药物能够从早期内涵体中逸出，从而进入细胞内环境。现场增加甲氨蝶呤负载的聚合物囊泡能够完全消除滑膜炎症并防止疾病进展和严重程度。总体而言，体外和体内研究揭示了聚合物囊泡作为治疗关节炎炎症的有前途的纳米疗法的潜力。
Using a preclinical in vivo model of arthritis and the gold standard disease-modifying anti-rheumatic drug, methotrexate, pH-responsive phosphorylcholine polymersomes, elicit both anti-inflammatory and anti-arthritic therapeutic efficacy, while drastically minimizing off-target toxicity. First, the selective accumulation of polymersomes within synovium of inflamed joints. Second, the polymersomes targeting ability toward activated macrophages and synoviocytes, via scavenger receptors, allow their uptake via endocytosis. And third, the polymersomes pH-responsiveness enables the drug escape from early endosomes and hence its intracellular milieu delivery. On-site augment of methotrexate loaded polymersomes enable the complete abrogation of synovial inflammation and prevent the disease progression and severity. Overall, in vitro and in vivo investigations reveal the potential of polymersomes as a promising nanotherapy for treating arthritic inflammation.