Mild Hyperthermia Induced by Gold Nanorod-Mediated Plasmonic Photothermal Therapy Enhances Transduction and Replication of Oncolytic Adenoviral Gene Delivery

Oncolytic adenovirus (Ad) is a promising candidate for cancer gene therapy. However, as a monotherapy, it has shown insufficient therapeutic efficacy in clinical trials. In this work, we demonstrate that gold nanorod (GNR)-mediated mild hyperthermia enhances the cellular uptake and consequent gene expression of oncolytic Ad to head and neck tumor cells. We examined the combination of oncolytic Ad expressing vascular endothelial growth factor promoter-targeted artificial transcriptional repressor zinc-finger protein and GNR-mediated mild hyperthermia to improve antitumor effects. The in vitro mechanisms of increased transduction in the presence and absence of hyperthermia were explored followed by evaluation of efficacy of this combination strategy in an animal model. Exposure to optimized hyperthermia conditions improved endocytosis of oncolytic Ad, transgene expression, viral replication, and subsequent cytolysis of head and neck cancer cells. GNR-mediated plasmonic photothermal therapy resulted in precise control of tumor temperature and induction of mild hyperthermia. A combination of oncolytic Ad and GNRs resulted in potent tumor growth inhibition of head and neck tumors.