Precisely Striking Tumors 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 tumors, but it remains a great challenge to conquer due to random drug diffusion and tumor complexity. Herein, we show that hyperthermia in mitochondria, an interparticle plasmonic coupling effect activated nanoevent, selectively strikes tumor tissues without damaging adjacent normal tissues. 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 tissues. In vivo study revealed that the temperature increment in tumor tissue with irradiation was nearly 4-fold 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.