Stable Black Phosphorus Nanosheets Exhibiting High Tumor-Accumulating and Mitochondria-Targeting for Efficient Photothermal Therapy via Double Functionalization.

Black phosphorus (BP) has exhibited excellent biocompatibility and high photothermal conversion efficiency under near-infrared light, which makes it very promising for photothermal therapy. However, practical applications are highly hampered because it lacks a targeting property and rapidly degrades in cancer cells, especially in response to strong intracellular oxidative stress. Here, we reported that the mitochondrial targeting peptide functionalized black phosphorus nanosheets covered with an acid-labile polymer shell (doubly functionalized black phosphorus (DFBP) nanosheets) exhibited good stability. DFBP nanosheets not only have excellent ability of accumulating in tumor tissue via surface charge switching but also can target mitochondria. The doubly functionalized black phosphorus nanosheets resulted in robust cancer cell uptake but very poor normal cell accumulation. In vivo , the BP nanosheets could highly accumulate in a tumor and specifically target mitochondria, generating enough hyperthermia under near-infrared light, leading to cell death. This work provides a powerful way to ablate a tumor selectively with negligible side effects.