Carrier-Free Nanodrugs for the Treatment of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is among the most prevalent malignancies worldwide and has high incidence and mortality rates. Conventional therapeutic modalities are constrained by substantial limitations in both efficacy and safety. Carrier-free nanodrugs, constructed through co-assembly of drugs and non-pharmacologically active ingredients without extra nanocarriers, have emerged as safe and promising drug delivery systems for HCC therapy. They feature facile fabrication, high drug loading capacity, synergistic therapeutic efficacy, and reduced carrier-associated toxicity, thereby offering an innovative strategy to address the current impasse in HCC treatment. Drawing upon recent literature, this review systematically summarizes advances in carrier-free nanodrugs for HCC treatment from the perspective of construction principles and assembly strategies, encompassing drug-drug co-assembly, drug-bioactive molecule co-assembly, drug-functional component co-assembly, and metal ion coordination co-assembly. Additionally, existing challenges along with future trends of carrier-free nanodrugs are critically discussed, aiming to provide valuable insights for the rational design of next-generation carrier-free nanodrugs against HCC.