Calcium Phosphate Mineralized Black Phosphorous with Enhanced Functionality and Anticancer Bioactivity

Biodegradable inorganic nanomaterials have opened new perspectives for cancer therapy due to their inherent anticancer activity. Black phosphorus nanosheets (BPs) with their unique bioactivity have recently been identified as promising cancer therapeutic agents but their application is hampered by the difficulty in surface functionalization. Herein, an in situ calcium phosphate (CaP) mineralization strategy is described to enhance the anticancer activity of BPs. By using BPs as the phosphate sources and growth templates, the synthesized CaP-mineralized BPs (CaBPs) retain the intrinsic properties of BPs and at the same time have high loading capacities for various fluorophores to enable effective bioimaging and tracing. Compared to BPs, CaBPs exhibit enhanced and selective anticancer bioactivity due to the improved pH-responsive degradation behavior and intracellular Ca²⁺ overloading in cancer cells. Furthermore, CaBPs specifically target mitochondria and cause structural damage, thus leading to mitochondria-mediated apoptosis in cancer cells. After intravenous injection, CaBPs target orthotopic breast cancer cells to inhibit tumor growth without giving rise to adverse effects or toxicity. The results demonstrate the great potential of CaBPs as targeted anticancer agents and the CaP mineralization approach provides a versatile surface functionalization strategy for nanotherapeutic agents.