Hyperthermia (HT) is currently used as a non-invasive technique for cancer therapy, whereby biological tissues are exposed to higher than normal temperatures, for selective ablation of tumoral cells. Heating treatments can be applied using external heating sources such as ultrasounds, however, heating only malignant cells selectively is difficult to obtain, and therefore the translation of this modality to the clinic is still challenging. Recently, there has been a growing interest in the use of gold nanoparticles (AuNPs) to selectively generate heat in a spatiotemporal fashion, which is known as photothermal therapy (PTT). The rationale for such therapy is based on the fact that metallic NPs can be synthetized to absorb incident light coming from a laser outside the body and generate heat only in the tissues where NPs are allocated. Moreover, AuNPs are highly biocompatible and can be finely tuned to absorb light in the near-infrared (NIR) spectral range, known as the “biological window” (690-1100 nm). In this range tissue is maximally transparent, and therefore, the light itself would not damage the tissue.
While significant efforts have been made to develop suitable NPs with appropriate heating capabilities, to date, the molecular mechanisms underlying the in vivo cellular responses to heat stress remain unclear.
Therefore, the overall aim of the HyHeat project is to use an invertebrate model (Hydra vulgaris) to screen the heating capabilities of different AuNPs in vivo, with the grand aim of understanding the cellular responses to heat stress and therefore taking the first steps towards improving nanoparticle mediated HT efficacy for therapeutic purposes. A simple invertebrate organism have been used, in line with European strategies aimed to reduce vertebrate experimentation. During the project, we have synthesized different types of AuNPs and fully characterized them. The toxicity in the animals have been assessed using different techniques, before proceeding to laser irradiation. Lastly, gene expression profiling after laser irradiation in Hydra has been performed. It has been possible to characterize the heating capabilities of the AuNPs in vivo and select deregulated genes upon irradiation.
