(A) Simplified Jablonski diagram describing the different energy transfer mechanisms involved in PTT. PTA: photothermal transduction agent, ICS: intersystem crossing. (B) Schematic illustration of the PTT process. Photothermal transduction agents (PTAs) are taken up by endocytosis and trapped into the endosomes. After NIR irradiation, PTAs absorb the light energy and transform it into heat, which could lead to endosomal escape by two major mechanisms. In the first one, also known as the heating effect leads to the destabilization of endosomal membranes by a localized increase in temperature. In the second one, the released heat is high enough to generate a vapor layer surrounding the PTAs such that it expands as a vapor nanobubble (VNB) that eventually collapses to induce endocytic membrane disruption. (Created with BioRender.com).