Mass Spectrometry Imaging Reveals Biodistribution and Biotransformation of Black Phosphorus

Black phosphorus (BP) holds significant potential in biomedicine, biosensing, and phototherapy; however, its instability and the poor understanding of its in vivo fate have limited its applications. Here, we developed an integrated label-free mass spectrometry imaging (MSI) platform to investigate BP's in vivo distribution, transformation, clearance, and metabolism in tumor-bearing mice. We detected BPs and related nitrogen/oxygen-containing phosphorus (P) clusters in six organs and tumor tissues, revealing distinctive tissue distributions. BP and its degradation products primarily accumulated in the liver and spleen, with the liver showing a radial distribution pattern around hepatic lobules. Notably, BP and related clusters can cross the blood-brain barrier into brain parenchyma. We further establish the in vivo transformation and metabolic pathways of BPs. Cellular experiments confirmed that nitric oxide synthase (NOS)-mediated nitric oxide (NO) generation drives BP nitridation during its transformation and metabolism under physiological conditions. This work not only provides vital information for biomedical applications of BP, but also establishes a platform for understanding in vivo translocation and transformation of nanomaterials, aiding their biosafety and health impact assessments.