Smart self-assembly of a multifunctional theranostic nanozyme for self-enhanced precise chemo/chemodynamic therapy

The use of hypoxia-activated prodrugs to treat breast cancer is a promising therapeutic strategy, but limited by inconsistent hypoxia states in whole tumors. Herein, we developed a theranostic nanozyme using Mn²⁺-driven self-assembly of fluorenylmethyloxycarbonyl-protected cysteine (Fmoc-Cys) as a multifunctional carrier for the first time, and co-encapsulated with tirapazamine (TPZ) and glucose oxidase (GOX). The prepared nanozyme is sensitive to excess glutathione (GSH) and achieves efficient self-enhanced chemo/chemodynamic therapy (CDT) thanks to the synergistic effect among the multiple components. The encapsulated GOX could consume oxygen, which promoted the activation of TPZ in normoxic tumor regions, and generate excessive H₂O₂, which enhanced the CDT effect of Mn²⁺. Meanwhile, the release of Mn²⁺ was ideal for T1 magnetic resonance imaging (MRI), and the fluctuations of sO₂ could be monitored by photoacoustic imaging (PAI). Therefore, this work presents a smart self-assembly nanozyme capable of dual-modality imaging and self-enhanced combined therapy.