In vivo real-time tracking of tumor-specific biocatalysis in cascade nanotheranostics enables synergistic cancer treatment

Abstract

Glucose oxidase (GOD)-based synergistic cancer therapy has aroused great research interest in the context of cancer treatment due to the inherent biocompatibility and biodegradability. However, this emerging therapeutic system still lacks a strategy to predict and regulate the in vivo biocatalytic behavior of GOD in real time to minimize the side effects on normal tissues. Herein, we developed a tumor-specific cascade nanotheranostic system (BNG) that combines GOD-catalyzed oxidative stress and dual-channel fluorescent sensing, significantly improving the synergistic therapeutic efficacy with real-time feedback information. The nanotheranostic system remains completely silent in the blood circulatory system and selectively releases GOD enzymes in the tumor site, with enhanced near-infrared (NIR) fluorescence at 825 nm. Subsequently, GOD catalyzes H₂O₂ production, triggering cascade reactions with NIR fluorescence at 650 nm as an optical output, along with GSH depletion, enabling synergistic cancer treatment. The designed nanotheranostic system, integrated with tumor-activated cascade reactions and triggering a dual-channel output at each step, represents an insightful paradigm for precise cooperative cancer therapy.