Radiotherapy-Induced Cleavage of Quaternary Ammonium Groups Activates Prodrugs in Tumors

摘要

Cleavage chemistry offers a new chance to activate chemotherapeutic prodrugs in a tumor-selective manner,yet developing spatiotemporally controllable cleavage chemistry with deep tissue penetration is still a great challenge.Herein,we present a novel radiotherapy-triggered cleavage chemistry that enables controlled drug release in tumors.Quaternary ammonium groups are identified as masking groups that can be efficiently removed by hydrated electrons(e~-_(aq))from water radiolysis.The subsequently released tertiary amines can be anti-cancer toxins or readily release functional molecules via 1,6-elimination.This radiotherapy-induced cleavage works successfully in living cells and tumor-bearing mice,showing remarkable treatment efficacy when the mice are given carfilzomib prodrug and radiotherapy.This strategy provides a new perspective for combinational radiochemotherapy,which is the first-line treatment for over 50 of cancer patients.