COF-based nanoreactors for click-activated prodrug delivery and precise anti-vascular therapy.

Herein, we report a new click-activated prodrug, CA4V, and a bioorthogonal nanoreactor, CA4V/ZIF-90@TzCOF@Apt, which consists of a ZIF-90 core, tetrazine-based covalent organic framework (COF) shells and an aptamer polymer coating. When targeting a tumor, the acid-causing collapse of ZIF-90 initiates a nanoconfined bioorthogonal reaction in defined COF cages, which boosts the click efficiency of CA4V activation and therapeutic effects in vivo .