Hepatic ischemia-reperfusion injury (IRI) is mainly driven by excessive production of reactive oxygen species (ROS) by mitochondria, and it is an important cause of liver dysfunction, graft failure, and postoperative complications. However, there are currently no approved drugs for its prevention or treatment, and effective therapeutic strategies urgently need to be developed. This study constructed a nanoplatform composed of polyethylene glycolylated polydopamine nanoparticles (PDA NPs) and mitochondrial-targeting peptide SS-31 (PPS NPs). The SS-31 peptide modification endows PPS NPs with efficient mitochondrial targeting ability, thereby restoring mitochondrial membrane potential and reducing ROS accumulation in the hypoxia/reoxygenation model. Moreover, PPS NPs treatment can significantly alleviate liver injury caused by IRI in mice, reduce inflammatory factor levels, and inhibit neutrophil infiltration. Transcriptome sequencing and metabolomics analysis indicated that PPS NPs can exert liver protection by maintaining mitochondrial structural integrity, reducing ROS production, and regulating arachidonic acid and glutathione metabolism. By maintaining mitochondrial function, stabilizing cellular redox homeostasis, and inhibiting inflammatory cascades, PPS NPs ultimately block the mitochondrial-dependent apoptotic pathway, providing effective protection against hepatic IRI and offering a feasible therapeutic strategy for the prevention and treatment of hepatic IRI in clinical settings. This study was published in ACS Nano under the title "Protective Effect of Mitochondria-Targeted Polydopamine Nanoparticles in Alleviating Hepatic Ischemia-Reperfusion Injury".
References:

DOI: 10.1021/acsnano.5c13406