Enhancing of plasmonic photothermal therapy through heat-inducible transgene activity

We explore the synergistic effect of photothermal therapy and gene therapy, simultaneously triggered by silica-gold nanoshells (NS) or hollow gold nanoparticles (HGNPs) in human HeLa cells following near-infrared (NIR) light irradiation. Thermal transfer from NS was higher than that displayed by HGNPs, owing to a differential interaction of the nanomaterial with the biological environment. Under sublethal photothermal conditions, NS and HGNPs effectively modulated the expression levels of a DsRed-monomer reporter gene controlled by the highly heat-inducible human HSP70B promoter, as a function of nanomaterial concentration and length of laser exposure. Hyperthermia treatments at doses that do not promote cell death generated a lethal outcome in HeLa cells harboring the fusogenic GALV-FMG transgene under the control of the HSP70B promoter. Combination of lethal photothermia with the triggering of the cytotoxic transgene resulted in a dramatic increase of the cell-ablation area as a result of the synergistic activity established.From the Clinical EditorIn this study photothermal therapy and gene therapy, simultaneously triggered by silica-gold nanoshells or hollow gold nanoparticles, was investigated in human HeLa cells following near-infrared (NIR) light irradiation. It is shown that the combination of lethal photothermia with the triggering of the cytotoxic transgene at sublethal levels results in a synergistic cytotoxic effect in vitro.

Graphical AbstractThe optical properties of gold nanoshells (NS) and hollow gold nanoparticles (HGNPs) can tune the expression of an antiproliferative transgene (GALV-FMG, hyperfusogenic form of membrane glycoprotein gene of gibbon-ape leukemia virus) controlled by the human heat-responsive HSP70B promoter. The synergistic effect of GALV-FMG activity and plasmonic photothermia amplifies the spatial restriction of photoablation.Figure optionsDownload high-quality image (192 K)Download as PowerPoint slide