Extraspecific Manifestation of Nanoheater’s Position Effect on Distinctive Cellular Photothermal Responses

Subcellular localization of nanoparticles plays critical roles in precision medicine that can facilitate an in-depth understanding of disease etiology and achieve accurate theranostic regulation via responding to the aiding stimuli. The photothermal effect is an extensively employed strategy that converts light into heat stimulation to induce localized disease ablation. Despite diverse manipulations that have been investigated in photothermal nanotheranostics, influences of nanoheaters’ subcellular distribution and their molecular mechanism on cellular heat response remain elusive. Herein, we disclose the biological basis of distinguishable thermal effects at subcellular resolution by localizing photothermal upconversion nanoparticles into specific locations of cell compartments. Upon 808 nm light excitation, the lysosomal cellular uptake initialized by poly(ethylenimine)-modified nanoheaters promoted mitochondria apoptosis through the activation of Bid protein, whereas the cell surface nanoheaters anchored via metabolic glycol biosynthesis triggered necrosis by direct perturbation of the membrane structure. Intriguingly, these two different thermolyses revealed similar levels of heat shock protein expression in live cells. This study stipulates insights underlying the different subcellular positions of nanoparticles for the selective thermal response, which provides valuable perspectives on optimal precision nanomedicine.