Self-Boosting Programmable Release of Multiple Therapeutic Agents by Activatable Heterodimeric Prodrug-Enzyme Assembly for Antitumor Therapy.

ABSTRACT: Endogenous stimuli-responsive prodrugs, due to their disease lesion specificity and reduced systemic toxicity, have been widely explored for antitumor therapy. However, reactive oxygen species (ROS) as classical endogenous stimuli in the tumor microenvironment (TME) are not enough to achieve the expected drug release. Herein, a ROS-activatable heterodimeric prodrug-loaded enzyme assembly is developed for self-boosting programmable release of multiple therapeutic agents. The heterodimeric prodrug NBS-TK-PTX (namely NTP) is composed of 5-(ethylamino)-9-diethylaminobenzo[a]phenothiazinium chloride analog (NBS), paclitaxel (PTX) and ROS-responsive thioketal (TK) linker, which shows a strong binding affinity with glucose oxidase (GOx), thus obtaining NTP@GOx assembly. Notably, the enzymatic act

SUBMITTER: Jiang S 

PROVIDER: S-EPMC11727268 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature