NANODIAMOND-BASED DRUG DELIVERY PLATFORM FOR SALL4-DRIVEN HEPATOCELLULAR CARCINOMA THERAPY

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Diverse oncogene drivers are involved in the its progression, whereas currently there are no target drugs available. Emerging therapeutic modalities combined with nanotechnology provide potential therapeutic options for HCC treatment. As such, a type of biocompatible carbon nanomaterials, nanodiamonds were investigated as a drug delivery platform for enhanced therapies against SALL4-driven HCC. Mediated by nanodiamonds, SALL4 siRNA showed enhanced tumor penetrative capability, gene knockdown efficiency and tumor inhibitory effect in HCC 3D models. Furthermore, a nanodiamond-based biosensor was developed for specific gene detection in HCC cells. Based on this, we established an AI-assisted platform for rapid evaluation of drug sensitivity. This platform could be applied for selection of SALL4hi patients that might respond to specific class of drugs. In general, our work demonstrates nanodiamonds can help to target the “undruggable” targets in HCC.