It is crucial but of a great challenge to study in vivo and in situ drug release of nanocarriers when developing a nanomaterial-based drug delivery platform. We developed a new label-free laser desorption/ionization mass spectrometry (MS) imaging strategy that enabled visualization and quantification of the in situ drug release in tissues by monitoring intrinsic MS signal intensity ratio of loaded drug over the nanocarriers. The proof of concept was demonstrated by investigating the doxorubicin (DOX)/polyethylene glycol–MoS₂ nanosheets drug delivery system in tumor mouse models. The results revealed a tissue-dependent release behavior of DOX during circulation with the highest dissociation in tumor and lowest dissociation in liver tissues. The drug-loaded MoS₂ nanocarriers are predominantly distributed in lung, spleen, and liver tissues, whereas the accumulation in the tumor was unexpectedly lower than in normal tissues. This new strategy could also be extended to other drug-carrier systems, such as carbon nanotubes and black phosphorus nanosheets, and opened a new path to evaluate the drug release of nanocarriers in the suborgan level.

Phosphonyl tyrosine is one of the main biomarkers to confirm exposure to highly lethal organophosphorus nerve agents (OPNAs) in vivo. However, a critical challenge remains unresolved: ionization suppression occurs during the analysis of phosphonyl tyrosine by high-resolution mass spectrometry (HRMS) or tandem mass spectrometry (MS/MS), which is induced by the high concentrations of free amino acids present in the digestion solution. In this study, based on the broad-spectrum immunomagnetic beads with high affinity antibodies, a non-targeted early warning and verification strategy was developed. Compared with the recommended operating procedures for analysis in the verification of chemical disarmament, the total analysis time was reduced from several hours to about 30 min. Moreover, the detection sensitivity was increased by nearly one order of magnitude, and the detection limit (LOD) was 0.01 ng/mL. Furthermore, the screening strategy can cover all OPNAs listed as 1A.01, 1A.02 and 1A.03 in Schedule 1 of the CWC. Therefore, we have developed a rapid, sensitive, and broad-spectrum approach to accurately screen for OPNAs exposure, while also offering a novel strategy and technical support for chemical defense and occupational health assessment.