MULTI-MODAL NANODIAMOND DRUG DELIVERY PLATFORM FOR SUBTYPE-SPECIFIC HEPATOCELLULAR CARCINOMA TREATMENT

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high mortality while limited therapeutic options. Diverse oncogene drivers and epigenetic regulators are involved in HCC progression. Traditional therapeutic modalities targeting specific oncogenes meet several challenges. As such, a novel and biocompatible carbon nanomaterial, nanodiamond (ND), was utilized as the drug delivery platform for enhanced therapies against HCC driven by oncogene SALL4 (Spalt Like Transcription Factor 4) and epigenetic regulator G9a (euchromatic histone-lysine N-methyltransferase 2). Overall, ND-drug complexes showed improved solubility, stability, and tissue specificity. Therapeutic efficacy was also enhanced both in vitro and in vivo, compared to the unmodified drug molecules. In general, our work demonstrates the potential for ND in clinical applications for treatment and diagnosis of subtype-specific HCC, paving the way of translating peptide, small-molecule inhibitor, as well as small interfering RNA (siRNA) in HCC treatment and metastasis detection.