Biomimetic macrophage membrane-camouflaged curcumin nanocrystals attenuate myocardial fibrosis after myocardial infarction

Myocardial infarction is one of the leading causes of heart failure. Following myocardial infarction, activated intrinsic immunity and an inflammatory response secrete various growth factors that contribute to the activation and proliferation of myocardial fibroblasts, inducing uncontrollable neo-dysfunction and heart failure. The transforming growth factor β1 (TGF-β1)/Smad signaling pathway is closely associated with ventricular remodeling and fibrosis post-myocardial infarction. Curcumin (CUR) inhibits the activation of the TGF-β1/Smad signaling pathway and collagen synthesis to alleviate heart fibrosis. However, its clinical applicability is hampered by its low bioavailability and poor water solubility. As a hydrophilic polymer, Polyvinylpyrrolidone K90 (PVP K90) can interact with CUR molecules to increase the solubility of CUR in water and improve the problem of its poor water solubility. Hence, in this work, we prepared curcumin nanocrystals (CN) used CUR and K90 by the method of solvent-exchange precipitation, which greatly increased the specific surface area and thus improved the dissolution properties. Subsequently, we prepared biomimetic CN by utilizing the chemotaxis of macrophages to regions of inflammation and extracting CN encapsulated within macrophage membranes (MCN). The outstanding characteristics of MCN were observed by transmission electron microscopy, FTIR and ultraviolet spectrophotometer. According to the cell uptake results, the macrophage membrane-coated nanoparticles were more effective in reaching RAW264.7 cells and the inflammatory damage sites. Further, the results of cardiac ultrasound and pathological staining demonstrated that MCN can alleviate the inflammatory area after infarction, facilitating the transport and release of CUR to the myocardial infarction site. The mechanism is attributed to MCN inhibiting the TGF-β1/Smad signaling pathway and improving myocardial fibrosis. Our findings offer a fresh approach to cardiac fibrosis medication treatment. This "inflammation-oriented" active targeting strategy provides a completely biomimetic concept for the precise intervention of myocardial fibrosis.