Revealing the immune perturbation of black phosphorus nanomaterials to macrophages by understanding the protein corona

The increasing number of biological applications for black phosphorus (BP) nanomaterials has precipitated considerable concern about their interactions with physiological systems. Here, we demonstrate the adsorption of plasma protein onto BP nanomaterials and the subsequent immune perturbation effect on macrophages. Using liquid chromatography tandem mass spectrometry, we discovered that BP nanosheets (BPNSs) were able to bind 23.3 percent of immune proteins from plasma, while BP quantum dots (BPQDs) bound 41.8 percent of immune proteins. In particular, the protein corona dramatically reshaped BP nanomaterial-corona complexes, influenced cellular uptake, activated the NF-κB pathway and even increased cytokine secretion by 2-5-fold. BP nanomaterials induced immunotoxicity and immune perturbation in macrophages in the presence of a plasma corona. These findings offer important insights into the development of safe and effective BP nanomaterial-based therapies.