Mitochondrial-Targeted Gold-Doped Porous Carbon Nanodots for Combined Photothermal and Photodynamic Therapy of Breast Cancer

Mitochondrial homeostasis has been proved to be a potential oncology therapeutic target, but there is still a huge technical challenge in developing an effective therapeutic regimen in clinic. Here, we developed triphenylphosphonium conjugated gold-doped porous carbon dots with 5-aminolevulinic acid (ALA) loading (T-CDs@Au/ALA nanodots) for mitochondrial-targeting combined therapy of breast cancer. Gold doping not only significantly enhanced the photothermal effect of T-CDs@Au/ALA nanodots but also enabled ALA (photosensitizer prodrug) loading via coordination interaction. Upon cellular internalization, the resultant T-CDs@Au/ALA nanodots were selectively enriched in the mitochondria and depleted glutathione, thus amplifying the reactive oxygen species damage caused by the accumulation of ALA-derived PpIX. Moreover, T-CDs@Au/ALA nanodots caused hyperthermia to further disrupt mitochondrial homeostasis for inducing the necrosis and apoptosis of tumor cells. Our study revealed that T-CDs@Au/ALA nanodots could use as an innovative mitochondrial homeostasis destroyer for synergistic phototherapy of breast cancer.