Palladium-catalyzed <i>in vivo</i> bioorthogonal activation of <i>N</i>,<i>N</i>-dialkyl-α-hydroxymethyl acrylamide for efficient payload release

The use of drug carriers plays a crucial role in ensuring the stable circulation of therapeutic agents within biological systems and their targeted delivery to specific sites, thereby enabling precise drug treatment. In this study, we developed a novel drug release carrier based on the structure of α-hydroxymethyl acrylamide. This carrier is capable of rapidly cleaving bonds and releasing the active payload (>90%) under the catalysis of the Pd (0) complex. When conjugated with the drug, the carrier demonstrated significant antitumor efficacy in a mouse tumor model. Overall, this innovative "click to release" chemistry exhibits fast kinetics and high efficiency, offering a promising new approach for drug delivery and prodrug release.