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.
Department of Bioengineering, College of Engineering, Hanyang University , 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Korea.
Bo-Kyeong
BK
Jung
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, Korea.
Yeon Kyung
YK
Lee
Department of Bioengineering, College of Engineering, Hanyang University , 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Korea.
JinWoo
J
Hong
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.
Hamidreza
H
Ghandehari
Department of Bioengineering, College of Engineering, Hanyang University , 222 Wangsimni-ro, Seongdong-gu, Seoul 133-791, Korea.
Chae-Ok
CO
Yun
D000256:Adenoviridae; D000818:Animals; D045744:Cell Line, Tumor; D006046:Gold; D006979:Hyperthermia, Induced; D043942:Nanotubes; D010789:Phototherapy; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D006046:Gold
endocytosis; gold nanorods; head and neck cancer; hyperthermia; oncolytic adenovirus