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 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 and 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.