Rational Utilization of Black Phosphorus Nanosheets to Enhance Palladium‐Mediated Bioorthogonal Catalytic Activity for Activation of Therapeutics

Pd‐catalyzed chemistry has played a significant role in the growing subfield of bioorthogonal catalysis. However, rationally designing Pd nanocatalysts that show outstanding catalytic activity and good biocompatibility poses a great challenge. Herein, we propose an innovative strategy through exploiting black phosphorous nanosheets (BPNSs) to enhance Pd‐mediated bioorthogonal catalytic activity. Firstly, the electron‐donor properties of BPNSs enable in situ growth of Pd nanoparticles (PdNPs) on it. Meanwhile, due to the superb capability of reducing PdII, BPNSs can act as hard nucleophiles to accelerate the transmetallation in the decaging reaction process. Secondly, the lone pair electrons of BPNSs can firmly anchor PdNPs on their surface via Pd−P bonds. This design endows Pd/BP with the capability to retard tumor growth by activating prodrugs. This work proposes new insights into the design of heterogeneous transition‐metal catalysts (TMCs) for bioorthogonal catalysis. A novel strategy is applied to enhance palladium‐mediated bioorthogonal catalytic activity by using a powerful partner: black phosphorus (BP) nanosheets, which can accelerate the transformation of Pd2+ to Pd0 to boost the reaction cycle, thus achieving a superior decaging efficiency of prodyes and prodrugs.