Gold nanorods and nanoprisms mediate different photothermal cell death mechanisms in vitro and in vivo.

Photothermal therapy is an efficient method of inducing localized hyperthermia and can be achieved by using gold nanoparticles (AuNPs) as photothermal agents. Yet there are many hurdles to get over before this therapy can safely reach the clinics, including nanoparticles optimal shape and the accurate prediction of cellular responses. Here we describe the synthesis of gold nanorods and nanoprisms with similar surface plasmon resonances in the near infrared (NIR) and comparable photothermal conversion efficiencies, and characterize the response to NIR irradiation in two biological systems, melanoma cells and the small invertebrate Hydra vulgaris. By integrating animal to cell and molecular biology approaches, we show diverse outcome of nanorods and nanoprisms on the two systems, sustained by the elicitation of different pathways, from necrosis to programmed cell death mechanisms (apoptosis and necroptosis). The comparative multilevel analysis shows great accuracy of in vivo invertebrate models to predict overall responses to photothermal challenging, and superior photothermal performance of nanoprisms. Understanding the molecular pathways of these responses may help to develop optimized nanoheaters that, safe by design, may improve photothermal therapy efficacy for clinical purposes.