Macrophage-targeted black phosphorus nanocomposites inhibit renal fibrosis by disrupting the oxidative stress-inflammation cycle and improving fatty acid metabolism

Chronic kidney disease (CKD) represents a major clinical challenge due to its high prevalence and mortality rates. Unfortunately, there is still a lack of specific targeted intervention drugs available at present. Renal fibrosis is a primary contributor to the persistent advancement of CKD. Here, the inflammatory response chain triggered by macrophages and the progression of oxidative stress construct a vicious cycle that significantly exacerbates fibrosis progression. Therefore, specific targeted intervention in the cyclic feedback is of significant clinical importance for curbing fibrosis progression and improving CKD. In this study, we focus on targeted precision intervention of renal fibrosis using black phosphorus nanosheets (BPNSs) as carriers. By loading FK228, a product from our previous research, on the surface and modifying the outer layer with phosphatidylserine (PS), we achieve high specificity targeting and accumulation in the kidneys during the CKD process. The PS anchors to phosphatidylserine receptors on the surface of macrophages within the kidney, efficiently reacting to overloaded ROS in macrophages, inhibiting the progression of oxidative stress and exacerbation of inflammatory storms. Subsequently, the carrier decomposes to release the HDAC-specific small molecule inhibitor FK228, further blocking fibrosis progression, thereby effectively improving CKD.