Exploiting The Protein Corona: Coating Of Black Phosphorus Nanosheets Enables Macrophage Polarization Via Calcium Influx

Black phosphorus nanosheets (BPNSs) have substantially promoted biomedical nanotechnology due to their unique photothermal and chemotherapeutic properties. However, there is still a limited molecular understanding of the effects of bio-nano interfaces on BPNSs and the subsequent impacts on physiological systems. Here, it is shown that black phosphorus-corona complexes (BPCCs) could function as immune modulators to promote the polarization of macrophages. Mechanistically, BPCCs could interact with calmodulin to activate stromal interaction molecule 2 and facilitate Ca2+ influx in macrophages, which induced the activation of p38 and NF-kappa B and polarized M0 macrophages to the M1 phenotype. As a result, BPCC-activated macrophages show greater migration towards cancer cells, 1.3-1.9 times higher cellular cytotoxicity and effective phagocytosis of cancer cells. These findings offer insights into the development of potential and unique applications of corona on BPNSs in nanomedicine.