Multistage‐Responsive Dual‐Enzyme Nanocascades for Synergistic Radiosensitization‐Starvation Cancer Therapy

• DOI: 10.1002/adhm.202300118
• Publication Date: 2023-04-24T23:34:50Z
• Authors: Ming Zhao; Anni Zhu; Xueyun Zheng; Xiaomin Qian; Shujun Zhang; Chenyu Wu; Congwei Yu; Jiaheng Zhang; Jingchao Li
• Keywords: Cancer Therapy

Abstract Radiotherapy is a common cancer treatment approach in clinical practice, yet its efficacy has been restricted by tumor hypoxia. Nanomaterials‐mediated systemic delivery of glucose oxidase (GOx) and catalase (CAT) or CAT‐like nanoenzymes holds the potential to enhance oxygenation. However, they face challenge intermediate (hydrogen peroxide [H 2 O ]) escape during circulation if enzyme pair not closely placed largely decompose H , leading oxidative stress on normal tissues. In present study, oxygen‐generating nanocascade, n(GOx‐CAT) C7A constructed strategically placing an enzymatic cascade (GOx CAT) within polymeric coating rich hexamethyleneimine (C7A) moieties, reported. During blood circulation, remains predominantly non‐protonated achieving prolonged due low‐fouling surface. Once reaches site, acidic microenvironment (TME) induces protonation resulting positively charged surface for enhanced transcytosis. Moreover, GOx CAT are covalently conjugated into close spatial proximity (<10 nm) effective elimination. As demonstrated vivo results, achieves retention oxygenation, potent radiosensitization antitumor effects. Such dual‐enzyme nanocascade smart great enhancing hypoxia‐compromised therapies.