Folic-Acid-Terminated Black Phosphorus Nanosheets for Targeted Gene Delivery and Photothermal Therapy against Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) remains one of the deadliest cancers, with limited effective treatments for advanced stages. Our research identified that silencing the CRNDE (colorectal neoplasia differentially expressed) gene can inhibit HCC cell proliferation, migration, and chemotherapy resistance. To improve the therapeutic efficiency of shCRNDE (short hairpin RNA), we developed a multifunctional nanosystem, BP@PLL-SeSe-FA/shCRNDE, using a three-step strategy. First, the system targets hepatocellular cells via folic acid (FA) receptors. Next, shCRNDE is delivered to silence the CRNDE gene, inhibiting tumor progression. Finally, BP nanosheets trigger cell death through photothermal therapy (PTT) under near-infrared irradiation. The BP@PLL-SeSe-FA/shCRNDE nanosystem achieved a photothermal conversion efficiency of 46.05% and reduced tumor growth by more than 60% with minimal systemic toxicity. These results indicate their potential for targeted gene and PTT in liver cancer treatment.