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Vaccines 2014, 2(2), 216-227; doi:10.3390/vaccines2020216

HSP70 Promoter-Driven Activation of Gene Expression for Immunotherapy Using Gold Nanorods and Near Infrared Light

1
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA
2
Department of Translational Imaging, Houston Methodist Research Institute, Houston, TX 77030, USA
3
Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA
*
Author to whom correspondence should be addressed.
Received: 5 December 2013 / Revised: 25 February 2014 / Accepted: 10 March 2014 / Published: 25 March 2014
(This article belongs to the Special Issue Vaccine Adjuvants)
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Abstract

Modulation of the cytokine milieu is one approach for vaccine development. However, therapy with pro-inflammatory cytokines, such as IL-12, is limited in practice due to adverse systemic effects. Spatially-restricted gene expression circumvents this problem by enabling localized amplification. Intracellular co-delivery of gold nanorods (AuNR) and a heat shock protein 70 (HSP70) promoter-driven expression vector enables gene expression in response to near infrared (NIR) light. AuNRs absorb the light, convert it into heat and thereby stimulate photothermal expression of the cytokine. As proof-of-concept, human HeLa and murine B16 cancer cells were transfected with a HSP70-Enhanced Green Fluorescent Protein (EGFP) plasmid and polyethylenimine (PEI)-conjugated AuNRs. Exposure to either 42 °C heat-shock or NIR light induced significant expression of the reporter gene. In vivo NIR driven expression of the reporter gene was confirmed at 6 and 24 h in mice bearing B16 melanoma tumors using in vivo imaging and flow-cytometric analysis. Overall, we demonstrate a novel opportunity for site-directed, heat-inducible expression of a gene based upon the NIR-absorbing properties of AuNRs and a HSP70 promoter-driven expression vector.
Keywords: gold nanorod; HSP70 promoter; near infrared; immunotherapy; cancer gold nanorod; HSP70 promoter; near infrared; immunotherapy; cancer
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Andersson, H.A.; Kim, Y.-S.; O'Neill, B.E.; Shi, Z.-Z.; Serda, R.E. HSP70 Promoter-Driven Activation of Gene Expression for Immunotherapy Using Gold Nanorods and Near Infrared Light. Vaccines 2014, 2, 216-227.

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