Nanodelivery of panobinostat induces cell cycle arrest and apoptosis to suppress hepatocellular carcinoma growth in mice

Hepatocellular carcinoma (HCC), the predominant subtype of primary liver cancer, remains as a globally lethal malignancy with limited therapeutic options. Despite therapeutic efficacy of small-molecule inhibitors, the majority of HCC patients are still incurable due to suboptimal response rate and serious systemic toxicity. Panobinostat (PANO), a potent histone deacetylase (HDAC) small-molecule inhibitor, has established clinical efficacy in hematological malignancies. However, clinical application of PANO in solid tumors (e.g., HCC) is significantly hindered by <i>in vivo</i> delivery barriers. In the present study, we show that PANO triggers cell cycle arrest and apoptosis in HCC cells, demonstrating its therapeutic potential for this malignancy. We also develop a nanocarrier using folic acid-targeted polyethylene glycol-modified poly(lactic-co-glycolic acid) to facilitate <i>in vitro</i> and <i>in vivo</i> administration of PANO. In mice with orthotopically allografted HCC, the resultant PANO-loaded nanoformulation achieves potent antitumor efficacy, characterized by significant tumor cell death, remarkable tumor regression, and prolonged animal survival. These findings demonstrate a promising regimen based on nanodelivery of PANO for HCC therapy.