Calming Cytokine Storm in Pneumonia by Targeted Delivery of TPCA-1 Using Platelet-Derived Extracellular Vesicles

利用血小板衍生的细胞外囊泡靶向递送 TPCA-1 平息肺炎中的细胞因子风暴

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作者:Qingle Ma, Qin Fan, Jialu Xu, Jinyu Bai, Xiao Han, Ziliang Dong, Xiaozhong Zhou, Zhuang Liu, Zhen Gu, Chao Wang

Abstract

Pneumonia can cause high morbidity and mortality because of uncontrolled inflammation in the lung tissue. Calming the cytokine storm may be one key to saving the life of patients with severe pneumonia. Here, inspired by the intrinsic affinity of platelets to the site of inflammation, we have engineered platelet-derived extracellular vesicles (PEVs) for pneumonia-targeted drug delivery. It is demonstrated that PEVs that are easily generated from the activated platelets can selectively target pneumonia in the mouse model with acute lung injury (ALI). By loading with [5-(p-fluorophenyl)-2-ureido]thiophene-3-carboxamide (TPCA-1), which can inhibit the production of inflammatory factors, the PEVs significantly improve therapeutic benefits by inhibiting the infiltration of pulmonary inflammatory cells and calming local cytokine storm compared with the free drug-treated group. Furthermore, we find that PEVs could serve as a broad platform that can selectively target various inflammatory sites, including chronic atherosclerotic plaque, rheumatoid arthritis, and wounds associated with skin.

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