Dissecting the molecular mechanism of apoptosis during photothermal therapy using gold nanoprisms

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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.
This work was supported by the MAT2011-26851-CO2-01, MAT2011-26851-CO2-02 and SAF2011-25390, projects of the Spanish Ministry of Science and Innovation, the grant ERC-Starting Grant 239931-NANOPUZZLE project and Fondo Social Europeo (FSE; Gobierno de Aragón). P.d.P., J.M.F., and J.P. thank ARAID for financial support, S.G.M. thanks Marie Curie Intra-European Fellowship 328985-COCOPOPS, and B.P. thanks the Alexander von Humboldt Foundation for a fellowship. Work from W.J.P. was supported by HSFP project RGP0052/2012. nanopr