한빛사논문
Abstract
Bo-Kyeong Jung†⊥, Yeon Kyung Lee‡⊥, JinWoo Hong†, Hamidreza Ghandehari*‡§, and Chae-Ok Yun*†
† Department of Bioengineering, College of Engineering, Hanyang University, 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Korea
‡ Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Korea
§ Departments of Pharmaceutics and Pharmaceutical Chemistry and of Bioengineering, Center for Nanomedicine, Nano Institute of Utah, University of Utah, Salt Lake City, Utah 84112, United States
*Corresponding authors
⊥These authors contributed equally
Abstract
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.
Keywords: endocytosis; gold nanorods; head and neck cancer; hyperthermia; oncolytic adenovirus
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