title: Enhancing of plasmonic photothermal therapy through heat-inducible transgene activity.
abstract: 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.
  
  
  BACKGROUND
  In 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.
authors.affiliation: CIBER de Bioingeniería, Biomateriales y Nanomedicina, CIBER-BBN, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Cebrián
authors.forename: Francisco
authors.initials: F
authors.lastname: Martín-Saavedra
authors.forename: Leyre
authors.initials: L
authors.lastname: Gómez
authors.forename: Manuel
authors.initials: M
authors.lastname: Arruebo
authors.forename: Jesus
authors.initials: J
authors.lastname: Santamaria
authors.forename: Nuria
authors.initials: N
authors.lastname: Vilaboa
mesh_terms: D015316:Genetic Therapy; D006046:Gold / Q000008:administration & dosage / Q000737:chemistry; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D007259:Infrared Rays; D017989:Leukemia Virus, Gibbon Ape / Q000235:genetics; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D057145:Nanoshells / Q000008:administration & dosage* / Q000737:chemistry; D010789:Phototherapy; D011401:Promoter Regions, Genetic; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry; D019076:Transgenes
chemical_list: D018840:HSP70 Heat-Shock Proteins; C491129:HSPA7 protein, human; D006046:Gold; D012822:Silicon Dioxide