Development of Cyclooctyne-Nitrone Based Click Release Chemistry for Bioorthogonal Prodrug Activation both <i>In Vitro</i> and <i>In Vivo</i>.
Unlock the power of bioorthogonal chemistry! This groundbreaking study unveils a novel click-release system that rapidly liberates payloads with unparalleled efficiency, paving the way for transformative cancer treatments.
This research developed a strain-promoted alkyne-nitrone cycloaddition (SPANC)-based click-release chemistry, featuring a carbamate-linked release moiety that triggers spontaneous elimination after the click reaction. This system demonstrated rapid kinetics, high-yield payload release, and exceptional stability under both in vitro and cellular conditions. The researchers also established a facile synthesis of highly click-reactive nitrones, enabling the construction of a systematic substrate library and validating the broad applicability of this strategy. In 4T1 murine breast cancer models, the bioorthogonal prodrug activation strategy showed significant tumor suppression with favorable safety profiles, validating its potential for in vivo use.