Coordination-Driven Enhancement of Radiosensitization by Black Phosphorus via Regulating Tumor Metabolism

Coordination-driven surface modification is an effective strategy to achieve nanosystem functionalization and improved physicochemical performance. Black phosphorus (BP)-based nanomaterials demonstrate great potential in cancer therapy, but their poor stability, low X-ray mass attenuation coefficient, and nonselectivity limit the application in radiotherapy. Herein, we used unsaturated iridium complex to coordinate with BP nanosheets to synthesize a two-dimensional layered nanosystem (RGD-Ir@BP) with higher biostability. Ir complex improves the photoelectric properties and photoinduced charge carrier dynamics of BP, hence Ir@BP generated more singlet oxygen after X-ray irradiation. In in vivo experiments, with X-ray irradiation, RGD-Ir@BP effectively inhibited nasopharyngeal carcinoma tumor growth but with minor side effects. Additionally, based on untargeted metabolomics analysis, the combined treatment specifically down-regulated the tumor proliferative mark of prostaglandin E2 in cancer cells. In general, this study provides a design strategy of high-performance coordination-driven BP-based nanosensitizer in cancer radiotherapy.

Automated summary

The coordination-driven surface modification strategy was used to synthesize a high biostability two-dimensional layered nanosystem (RGD-Ir@BP) for cancer therapy. The nanosystem effectively inhibited nasopharyngeal carcinoma tumor growth with minor side effects in vivo, and down-regulated the tumor proliferative mark of prostaglandin E2 in cancer cells based on untargeted metabolomics analysis. This study provides a design strategy of high-performance coordination-driven BP-based nanosensitizer in cancer radiotherapy.