title: HSP70 promoter-driven activation of gene expression for immunotherapy using gold nanorods and near infrared light.
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.
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Andersson
authors.affiliation: Department of Translational Imaging, Houston Methodist Research Institute, Houston, TX.
authors.forename: Yoo-Shin
authors.initials: YS
authors.lastname: Kim
authors.affiliation: Department of Translational Imaging, Houston Methodist Research Institute, Houston, TX.
authors.forename: Brian E
authors.initials: BE
authors.lastname: O'Neill
authors.affiliation: Department of Translational Imaging, Houston Methodist Research Institute, Houston, TX.
authors.forename: Zheng-Zheng
authors.initials: ZZ
authors.lastname: Shi
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX ; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Rita E
authors.initials: RE
authors.lastname: Serda
keywords: HSP70 promoter; cancer; gold nanorod; immunotherapy; near infrared