Endosomal Confinement of Gold Nanospheres, Nanorods, and Nanoraspberries Governs Their Photothermal Identity and Is Beneficial for Cancer Cell Therapy

Gold nanoparticles can act as photothermal agents to generate local tumor heating and subsequent depletion upon laser exposure. Herein, photothermal heating of four gold nanoparticles and the resulting induced cancer cell death are systematically assessed, within extra‐ or intracellular localizations. Two state‐of‐the‐art gold nanorods are compared with small nanospheres (single‐core) and nanoraspberries (multicore). Heat generation is measured in water dispersion and in cancer cells, using lasers at wavelengths of 680, 808, and 1064 nm, covering the entire range used in photothermal therapy, defined as near infrared first (NIR‐I) and second (NIR‐II) windows, with NIR‐II offering more tissue penetration. When dispersed in water, gold nanospheres provide no significant heating, gold nanorods are efficient in NIR‐I, and only gold nanoraspberries are still heating in NIR‐II. However, in cells, due to endosomal confinement, all nanoparticles present an absorption red‐shift translating visible and NIR‐I absorbing nanoparticles into effective NIR‐I and NIR‐II nanoheaters, respectively. The gold nanorods then become competitive with the multicore nanoparticles (nanoraspberries) in NIR‐II. Similarly, once in cells, gold nanospheres can be envisaged for NIR‐I heating. Remarkably, nanoraspberries are efficient nanoheaters, whatever the laser applied, and the extra‐ versus intra‐cellular localization demonstrates treatment versatility.