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.

Temperature-Dependent CAT-Like RGD-BPNS@SMFN Nanoplatform for PTT-PDT Self-Synergetic Tumor Phototherapy.

Phototherapies such as photothermal therapy (PTT) and photodynamic therapy (PDT) are considered as alternatives for tumor remedies, because of their advantages of precise spatial orientation, minimally invasive, and nonradiative operation. However, most of phototherapeutic agents still suffer from low photothermal conversion efficacy and photodynamic performance, poor biocompatibility, and intratumor accumulation. Herein a biocompatible and target-deliverable PTT-PDT self-synergetic nanoplatform of RGD-BPNS@SMFN based on temperature-dependent catalase (CAT)-like behavior for tumor elimination is presented. The homogeneously dispersible nanoplatform is designed and fabricated through anchoring spherical manganese ferrite nanoparticles (SMFN) to black phosphorus nanosheets (BPNS), followed by arginine-glycine-aspartic acid (RGD) peptide modification. The nanoplatform exhibits excellent targeting ability and enhanced photonic response in comparison to plain BPNS and SMFN in vitro and in vivo. It is found that PTT and PDT have a self-synergetic behavior by means of the dual phototherapy mode interaction. The self-synergetic mechanism is mainly ascribed to PTT-promoted inherent CAT-like activity in the nanoplatform, which remodels the tumor hypoxia microenvironment and further ameliorates the PDT efficiency, providing promising high performance nanoplatform for synergetic dual mode phototherapy, enriching the design for the antitumor nanozyme.