Decitabine-Loaded Gold Nanocages for Photothermal Cancer Therapy via DNA Hypermethylation Reversal

Hypermethylation of tumor suppressor genes due to the aberrant expression of DNA methyltransferases (DNMT) is a key hallmark of cancer. However, the development of drugs targeting DNA methylation has lagged considerably. We designed a synergistic treatment against hepatocellular carcinoma (HCC) by combining photothermal therapy (PTT) with DNMT1 inhibitor-mediated chemotherapy. Decitabine-loaded gold nanocages (AuNCs) with PEGylated-T7 peptide surface modification (Au@Dec@T7) were synthesized. The Au@Dec@T7 NPs selectively accumulated at the tumor sites and ablated tumor cells following NIR irradiation. In addition, decitabine activated the tumor suppressor genes including p15 and E-cadherin that were epigenetically silenced due to PTT-induced hyperthermia and DNA hypermethylation. Finally, the NPs were biocompatible and did not cause any systemic toxicity. This study provides proof-of-concept for DNMT inhibitor-loaded NPs for targeted and effective synergistic PTT and chemotherapy against tumor growth.