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

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

Summary Pneumonia can cause high morbidity and mortality due to the uncontrolled inflammation in the lung tissue. Calming the cytokine storm may be one key to save 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 mice model with acute lung injury (ALI). By loading with [5-(p-Fluorophenyl)-2-ureido] thiophene-3-carboxamide (TPCA-1) that can inhibit the production of inflammatory factors, the PEVs significantly improve therapeutic benefits by inhibiting the pulmonary inflammatory cells infiltration, 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 wound associated with skin.