Photothermal biomodulation: a conceptual framework

Temperature is a fundamental driver of all chemical reactions, as expressed by the Arrhenius equation. This is also true in biology, where homeostasis and many other conditions are maintained in dynamic equilibrium by opposing biochemical processes. In principle therefore, it should be possible to use temperature to control any biochemical equilibrium, provided we can target heat sufficiently accurately to relevant reaction pathways. Photothermal effects mediated by nanoscale absorbers have emerged as a powerful means of controlling biological processes with light, with applications ranging from cancer treatments to neural interfaces. For example, gold nanoparticle-enhanced infrared neural modulation has achieved both stimulation and inhibition of retinal ganglion cells, suggesting that photothermal neuromodulation may be well-suited to future retinal prostheses. However, the counter-intuitive nature of nanoscale temperature distributions can present a conceptual barrier. A typical gold nanoparticle absorber is approximately 1000 times smaller than a cell and can return to thermal equilibrium with the surrounding environment within about 50ns after exposure to light, enabling heat delivery to localised cellular regions. Recent work has shown that functionalised gold nanoparticles can be accurately targeted to precise cellular locations, and the constrained intracellular environment appears relatively resistant to thermal damage on these timescales. Interestingly, some work has suggested that mitochondrial temperatures can reach 50°C. While this remains controversial, it seems plausible that waste heat from cellular respiration would cause transient temperature spikes. A complete understanding requires improved methods for measuring and modelling temperature distributions over wider spatial and temporal scales. The framework presented here aims to stimulate ideas for future work and inspire new strategies for exploiting these fundamental phenomena to address problems in medicine and biology.