title: Dissecting the molecular mechanism of apoptosis during photothermal therapy using gold nanoprisms.
abstract: The photothermal response of plasmonic nanomaterials can be exploited for a number of biomedical applications in diagnostics (biosensing and optoacoustic imaging) and therapy (drug delivery and photothermal therapy). The most common cellular response to photothermal cancer treatment (ablation of solid tumors) using plasmonic nanomaterials is necrosis, a process that releases intracellular constituents into the extracellular milieu producing detrimental inflammatory responses. Here we report the use of laser-induced photothermal therapy employing gold nanoprisms (NPRs) to specifically induce apoptosis in mouse embryonic fibroblast cells transformed with the SV40 virus. Laser-irradiated "hot" NPRs activate the intrinsic/mitochondrial pathway of apoptosis (programmed cell death), which is mediated by the nuclear-encoded proteins Bak and Bax through the activation of the BH3-only protein Bid. We confirm that an apoptosis mechanism is responsible by showing how the NPR-mediated cell death is dependent on the presence of caspase-9 and caspase-3 proteins. The ability to selectively induce apoptotic cell death and to understand the subsequent mechanisms provides the foundations to predict and optimize NP-based photothermal therapy to treat cancer patients suffering from chemo- and radioresistance.
authors.affiliation: Instituto Universitario de Nanociencia de Aragón (INA), Universidad de Zaragoza , 50018 Zaragoza, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pérez-Hernández
authors.forename: Pablo
authors.initials: P
authors.lastname: Del Pino
authors.forename: Scott G
authors.initials: SG
authors.lastname: Mitchell
authors.forename: María
authors.initials: M
authors.lastname: Moros
authors.forename: Grazyna
authors.initials: G
authors.lastname: Stepien
authors.forename: Beatriz
authors.initials: B
authors.lastname: Pelaz
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Parak
authors.forename: Eva M
authors.initials: EM
authors.lastname: Gálvez
authors.forename: Julián
authors.initials: J
authors.lastname: Pardo
authors.forename: Jesús M
authors.initials: JM
authors.lastname: de la Fuente
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002472:Cell Transformation, Viral; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology*; D007700:Kinetics; D007834:Lasers; D051379:Mice; D050997:Nanomedicine; D049329:Nanostructures; D010789:Phototherapy
chemical_list: D006046:Gold
keywords: Bcl-2 family; NIR window; apoptosis; gold nanoparticles; mitochondrial pathway; nanoprism; photothermal