Thermal dose as a universal tool to evaluate nanoparticle-induced photothermal therapy

Thermal isoeffect dose (TID) is a widely applied concept to evaluate the safety of medical devices that can expose patients to heat. However, it has rarely been used in photothermal therapy (PTT), where nanoparticles are used as light absorbers. Utilizing TID in an appropriate way would make it feasible to compare the results obtained with different light absorbers as well as clarifying their cellular effects. Herein, we apply TID as a definitive parameter to evaluate the outcomes of a nanoparticle-induced PTT in vitro. We show that cell death measured with an ATP-based viability assay and flow cytometry can be correlated with TID if time-temperature data is available. As an experimental model, black porous silicon nanoparticles were studied as photothermal agents to kill HeLa cancer cells. The results indicate that as the critical TID of 70 min is reached, the cells start to undergo apoptosis independently of the way in which the TID was attained: by long heating at low temperatures or by short heating at high temperatures. Overall, TID is proposed as a valid parameter which could be determined in the PTT studies to allow a straightforward comparison of the published results and the elucidation of the cell death mechanisms.