We have developed a GSH-triggered, activatable, and cancer-targeting probe, MBP, based on our rational design of a small NIRF photosensitizer, methylene blue. This multifunctional probe can self-assemble and present as nano-photosensitizer, MBNPs. Hence, an “all-in-one” cancer phototheranostic strategy with multiple cancer-targeting abilities and upgraded PDT mode has been proposed and established.

Isoxazole is an essential pharmacophore in drug discovery. In this study, we investigated the photochemistry of isoxazole with biomolecules and developed it as a natively embedded photo-cross-linker for chemoproteomics and drug discovery. With this strategy, two isoxazole-containing drugs were successfully applied to chemoproteomic platforms to uncover their cellular targets and interactions.

Tetrazole-based probes bearing an alkyne handle are suitable for phenotypic screening and affinity-based proteome profiling, especially Tz6, which can sensitively detect a cancer biomarker by both protein labeling and bioimaging.