Macrophage\nMembrane-Cloaked ROS-Responsive Albumin\nNanoplatforms for Targeted Delivery of Curcumin to Alleviate Acute\nLiver Injury

Developing low-toxicity, high-efficacy, and fast-acting\nstrategies\nto manage acute liver injury (ALI) is critical due to its rapid progression\nand potential for severe outcomes. Curcumin (CUR) has shown promise\nin ALI therapy due to its ability to modulate the inflammatory microenvironment\nby scavenging reactive oxygen species (ROS). Nevertheless, CUR is\nhighly hydrophobic limiting its bioavailability and effective in vivo\ntransport, which hinders its further application. In this study, we\ndeveloped an inflammatory microenvironment-targeted drug delivery\nsystem by covalently coupling human serum albumin (HSA) with ROS-sensitive\nthioketal linkers and loading it with CUR to form nanoparticles (HSA-TK/CUR).\nThese nanoparticles were then coated with a macrophage membrane (CM@HSA-TK/CUR),\nresulting in negatively charged spherical particles (≈ −23.26\nmV) with an average particle size of around 165 nm. ROS responsiveness\nwas confirmed through drug release assays and enhanced ROS depletion\nwas further demonstrated by Diacetyldichlorofluorescein (DCFH-DA)\nROS detection experiments. CM@HSA-TK/CUR treatment resulted in a 94.7%\nreduction in ROS levels in inflammatory cells. In addition, cellular\nuptake and in vivo distribution experiments demonstrated that camouflaging\nHSA-TK/CUR with macrophage membranes significantly enhanced its targeting\nof the inflammatory microenvironment. The findings revealed that CM@HSA-TK/CUR\nrapidly accumulated in the injured liver within 6 h, inhibited the\nproduction of pro-inflammatory factors (IL-1β, IL-6, and TNF-α),\nshifted macrophage polarization from M1 to M2 in vivo, and protected\nhepatocytes from oxidative stress-associated cell death, significantly\nattenuating the inflammatory response in ALI mice. In conclusion,\nCM@HSA-TK/CUR has excellent potential in treating mice with ALI.