D-peptide engineered hydrogel with dual-enzyme-ALA cascades enables multimodal oxygen modulation for self-sustaining EDT-PDT synergy.

Zhang, Qi; Zheng, Zhe; Zhao, Yiting; Wu, Qing; Wu, Chu; Wang, Xiuli; Wang, Xia; Wang, Qigang et al. · Bioact Mater · 2026

basic_science · Level V

Where this comes from

Abstract

The transformation of O<sub>2</sub> is primarily facilitated by the catalytic action of redox enzymes, which play a pivotal role in sustaining cellular energy metabolism and redox balance. Bioinspired by O<sub>2</sub> distribution and ROS regulation related to cascade biocatalytic process, a D-peptide NapG<sup>D</sup>F<sup>D</sup>F<sup>D</sup>Y engineered hydrogel has been constructed with encapsulated dual-enzyme superoxide (SOD) and chloroperoxidase (CPO) cascade catalytic circuit and co-assembled photosensitizer of 5-aminolevulinic acid molecules (ALA). Multimodal oxygen modulation has been conducted by the concurrent oxygen generation via SOD-catalyzed ⋅O<sub>2</sub> <sup>-</sup> dismutation and oxygen consumption for <sup>1</sup>O<sub>2</sub> production by CPO and ALA, achieving self-sustaining enzymatic dynamic therapy (EDT)-photodynamic therapy (PDT) (EDT-PDT) synergy. The endogenous cascade-amplified EDT not only enhances the <sup>1</sup>O<sub>2</sub> efficacy in exogenous PDT therapy, but the intermediate O<sub>2</sub> can also alleviate local neuropathic pain caused by hypoxia for safe PDT treatment. This work pioneers enzyme-mediated dynamic control of tumor redox homeostasis, establishing a new therapeutic axis between biocatalytic amplification and photodynamic processes.