Cationic Micelle as An In Vivo Catalyst for Tumor-Localized Cleavage Chemistry.

Wang, Chunhong; Hong, Hanyu; Chen, Mengqi; Ding, Zexuan; Rui, Yuchen; Qi, Jianyuan; Li, Zi-Chen; Liu, Zhibo

The emerging strategies of accelerating the cleavage reaction in tumor through locally enriching the reactants is promising. Yet, the applications are limited due to the lack of the tumor-selectivity for most of the reactants. Here we explored an alternative approach to leverage the rate constant by locally inducing an in vivo catalyst. We found that the desilylation-induced cleavage chemistry could be catalyzed in vivo by cationic micelles, and accelerated over 1400-fold under physiological condition. This micelle-catalyzed controlled release platform is demonstrated by the release of a 6-hydroxyl-quinoline-2-benzothiazole derivative (HQB) in two cancer cell lines and a NIR dye in mouse tumor xenografts. Through intravenous injection of a pH-sensitive polymer micelles, we successfully applied this strategy to a prodrug activation of hydroxyl camptothecin (OH-CPT) in tumors. Its "decaging" efficiency is 42-fold to that without cationic micelles-mediated catalysis. This micelle-catalyzed desilylation strategy unveils the potential that micelle may act beyond a carrier but a catalyst for local perturbing or activation.