Precisely Striking Tumor without Adjacent Normal Tissue Damage via Mitochondria-Templated Accumulation.

Ignored damage in adjacent normal tissue is fatal especially in some specific tumor therapy such as brain tumor, but it remains a great challenge to conquer it due to random drug diffusion and tumor complexity. Herein, we show the hyperthermia in mitochondria, an interparticle plasmonic coupling effect activated nanoevent, selectively strikes tumor tissue without damaging adjacent normal tissue. Spherical gold nanoparticles with a mitochondria-targeting moiety, triphenyl phosphonium, preferentially accumulated inside tumor mitochondria and reached the threshold to activate interparticle plasmonic coupling effect among gold nanoparticles, realizing selective light-thermal conversion and mitochondrial dysfunction in tumor, whereas little hyperthermia and mitochondrial dysfunction were observed in adjacent normal tissue. In vivo study revealed that the temperature increment in tumor tissue with irradiation was nearly 4 folds to that in adjacent normal tissue. This subcellular organelle-templated accumulation strategy provides a therapeutic model for highly selective tumor therapy with negligible local side effects.