Decitabine-Loaded Gold Nanocages for Photothermal Cancer Therapy via DNA Hypermethylation Reversal
Yan Sun, Songcai Liu, Yuan Gao, Yangyang Du, Hongqiao Cai, Jian Zhang, Zhaoguo Wang, Xi Yang, Linlin Hao, Fei Yan
Abstract
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.