Construction of curcumin-loaded macrophage and HUVECs membrane-derived vesicles for drug delivery in cardiovascular inflammatory

Abstract

In the progression of cardiovascular disease (CVD), myocardial inflammation and vascular endothelial inflammation are prevalent pathological phenomena. However, the development of drug delivery platform with high specificity against these inflammatory injury sites remains a challenge. To overcome this, we fused RAW264.7 macrophage membranes with human umbilical vein endothelial cell (HUVEC) membranes to prepare hybrid extracellular vesicles (RAW-HEVs) consisted of both types of cell membrane proteins. This hybrid EVs exhibited high uptake ratio towards LPS-induced inflammatory HUVECs and H9C2 cells. By leveraging the stealth properties of HUVEC membranes in the bloodstream and the innate inflammation-targeting ability of RAW264.7 macrophage membranes, RAW-HEVs actively accumulated at inflammatory sites of the heart and thoracic aorta in vivo. By loading curcumin (Cur) with anti-inflammatory activity to prepare Cur-loaded hybrid extracellular vesicles (RAW-H/Cur). RAW-H/Cur significantly reduced the expression of pro-inflammatory cytokines in cell supernatants and mice serum as compared to free Cur, as determined by ELISA. In addition, a significant reduction in LPS-induced organ damage in the heart and thoracic aorta was observed with RAW-H/Cur treatment, determined by Hematoxylin-eosin staining and immunohistochemistry. In conclusion, RAW-H/Cur, as a promising bionic delivery system for cardiovascular inflammatory diseases, is expected to help deliver Cur to inflamed regions of the heart and blood vessels and alleviate inflammatory symptoms.