Coordinating bioorthogonal reactions with two tumor-microenvironment-responsive nanovehicles for spatiotemporally controlled prodrug activation.

ABSTRACT: Precise activation of prodrugs in tumor tissues is critical to ensuring specific antitumor efficacy, meanwhile reducing the serious adverse effects. Here, a spatiotemporally controlled prodrug activation strategy was provided by integrating the inverse electron demand Diels-Alder (IEDDA) reaction with two tumor-microenvironment-responsive nanovehicles. The prodrug (Dox-TCO) and [4-(6-methyl-1,2,4,5-tetrazin-3-yl)phenyl]methanamine (Tz) were separately camouflaged into low pH and matrix metalloproteinase 2 (MMP-2) sensitive micellar nanoparticles. After systemic administration, only in the tumor tissues could both the nanovehicles dissociate via responding to two special tumor microenvironments, with Dox-TCO and Tz released and then immediately triggering the prodrug activation throu

SUBMITTER: Zuo L 

PROVIDER: S-EPMC8150104 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature