Chirality-Dependent Tumor Phototherapy Using Amino Acid-Engineered Chiral Phosphorene

Phosphorene, also known as black phosphorus nanosheet (BPNS), has been investigated as a nanoagent for tumor therapy. However, promoting its intracellular accumulation while preventing the cytoplasmic decomposition remains challenging. Herein, for the first time, we propose a chiral BPNS designed through surface engineering based on amino acids with high biocompatibility and an abundant source for application in chirality-dependent tumor phototherapy based on its intracellular metabolism. The advantage of using cysteine (Cys) over other amino acids was that its d, l, or dl -form could efficiently work as the chirality inducer to modify the BPNS through electrostatic interaction and prevent alterations in the intrinsic properties of the BPNS. In particular, d -Cys-BPNS displayed an approximately threefold cytotoxic effect on tumor cells compared with l -Cys-BPNS, demonstrating a chirality-dependent therapy behavior. d -Cys-BPNS not only promoted high intracellular content but also showed resistance to cytoplasmic decomposition. Cys-engineered BPNS also demonstrated chirality-dependent phototherapy effects on tumor-bearing mice, in proximity to the results in vitro . Chiral engineering is expected to open new avenues that could promote the use of BPNS in tumor phototherapy and boost chiral nanomedicine.