Bioorthogonal decaging chemistry with both fast kinetics and high efficiency is highly demanded for in vivo applications but remains very sporadic. Herein, we describe a new bioorthogonal decaging chemistry between -oxide and silylborane. A simple replacement of "C" in boronic acid with "Si" was able to substantially accelerate the -oxide decaging kinetics by 10 fold (: up to 10 M s). Moreover, a new -oxide-masked self-immolative spacer was developed for the traceless release of various payloads upon clicking with silylborane with fast kinetics and high efficiency (>90%). Impressively, one such -oxide-based self-assembled bioorthogonal nano-prodrug in combination with silylborane led to significantly enhanced tumor suppression effects as compared to the parent drug in a 4T1 mouse breast tumor model. In aggregate, this new bioorthogonal click-and-release chemistry is featured with fast kinetics and high efficiency and is perceived to find widespread applications in chemical biology and drug delivery.
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