Melanin Nanoparticle-Enabled Local Drug Delivery Platform for Preventing Postoperative Recurrence of Liver Cancer

Surgical resection is the main treatment for liver cancer. Despite chemotherapy (CT) is often used to reduce local recurrence, however, intravenously administered drugs often fail to reach effective concentrations in tumor tissues, causing significant side effects and reducing patient compliance. Herein, we have developed a multifunctional nanodrug platform (CINP-CuS@TD) by conjugating triphenylphosphine (TPP) and adsorbing doxorubicin (DOX) onto melanin nanoparticles embedded with copper sulfide nanocrystals (CINP-CuS). CINP-CuS@TD demonstrates a remarkable photothermal effect and Fenton-like catalytic activity, producing abundant reactive oxygen species (ROS) through photothermal therapy (PTT) and chemodynamic therapy (CDT). This multitherapeutic approach enhances the antitumor efficacy of DOX while reducing its required chemotherapy dosage. As validated in vivo liver cancer recurrence model, CINP-CuS@TD significantly inhibits tumor recurrence through the combined action of CDT, PTT, and CT. Consequently, CINP-CuS@TD holds potential as a local therapeutic agent for preventing postoperative recurrence and metastasis of liver cancer.