程序化DNAzyme纳米催化剂调控肿瘤免疫代谢

罗荣萍; 汤卓佳; 丁梦琪; 邹聆岫; 刘晓静; 尹凡; 吕建新; 王璐

doi:10.1631/jzus.B2500764

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Review | Updated：2026-07-29

程序化DNAzyme纳米催化剂调控肿瘤免疫代谢
Programmable DNAzyme nanocatalysts for tumor immunometabolic modulation
浙江大学学报（英文版）（B辑：生物医学和生物技术） 2026年27卷第7期页码：698-714
Affiliations：

1.School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou 311399, China
2.School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou 311399, China
3.Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, China
4.School of Public Health, Hangzhou Medical College, Hangzhou 311399, China
5.Zhejiang University-University of Edinburgh Institute, Haining 314400, China
6.Center of Clinical Laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou 310014, China
Funds：

the Seeking Truthful Talents Projects of Hangzhou Medical College(00004E1RCYJ2408);the Natural Science Foundation of Hangzhou(2025SZRJJ0037);the General Research Project of the Zhejiang Provincial Department of Education(Y202559865);the Joint Funds of the National Natural Science Foundation of China(U22A20342 to J.L)
DOI：10.1631/jzus.B2500764
中图分类号：
CSTR：
收稿：2025-11-24，

修回：2026-04-24，

网络首发：2026-07-29，

纸质出版：2026-07-15
Accepted：

罗荣萍,汤卓佳,丁梦琪等.程序化DNAzyme纳米催化剂调控肿瘤免疫代谢[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(07):698-714.

Rongping LUO, Zhuojia TANG, Mengqi DING, et al. Programmable DNAzyme nanocatalysts for tumor immunometabolic modulation[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(7): 698-714.
罗荣萍,汤卓佳,丁梦琪等.程序化DNAzyme纳米催化剂调控肿瘤免疫代谢[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(07):698-714. DOI： 10.1631/jzus.B2500764.

Rongping LUO, Zhuojia TANG, Mengqi DING, et al. Programmable DNAzyme nanocatalysts for tumor immunometabolic modulation[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(7): 698-714. DOI： 10.1631/jzus.B2500764.

摘要

RNA切割型DNAzyme是一类兼具分子识别能力和酶样催化活性的功能核酸分子，在靶向基因调控、生物传感和肿瘤治疗中具有重要应用潜力。近年来，随着纳米技术的发展，DNAzyme可与金属氧化物、DNA框架结构、金属有机框架等纳米平台集成，形成具有递送保护、金属辅因子供给和肿瘤微环境响应能力的程序化纳米催化体系。这类体系能够响应pH、氧化还原稳态、金属离子和microRNA等内源性信号，并将其转化为特异性RNA催化切割输出。本文系统综述了DNAzyme催化机制、序列与化学工程策略、纳米平台构建方式及其在肿瘤免疫代谢调控中的应用。重点讨论了DNAzyme纳米催化剂如何通过调节糖酵解、氧化还原稳态、线粒体功能、营养竞争及cGAS-STING相关免疫信号，缓解肿瘤免疫抑制并促进抗肿瘤免疫激活。最后，本文总结了该领域在体内递送、辅因子供给、催化特异性、生物安全性和标准化评价方面面临的转化挑战，并展望其作为生物传感引导的肿瘤免疫代谢干预平台的发展前景。

Abstract

Programmable RNA-cleaving DNAzymes (RCDs) represent a unique class of catalytic nucleic acids that couple molecular recognition with enzyme-like activity. While DNAzymes have traditionally been explored for targeted gene regulation

recent advances in nanotechnology have repositioned them as programmable biosensing modules with stimuli-responsive therapeutic potential. When integrated into metal-oxide scaffolds

DNA-framework architectures

or metal-organic frameworks

DNAzymes form hybrid platforms that create confined catalytic microenvironments

provide enriched cofactor availability

and facilitate microenvironment-responsive activation. These engineered systems can function as nanoscale biosensing modules that respond to pH

redox gradients

metal ions

or microRNA signatures and convert these biological cues into catalytic outputs. Beyond enhancing analytical performance

such platforms may also reshape tumor immunometabolism. Through the selective cleavage of metabolic or immune-regulatory transcripts

DNAzyme nanocatalysts can directly reprogram glycolysis

redox balance

oxygen tension

and mitochondrial activity

and these metabolic changes in turn alleviate immunosuppression and promote innate and adaptive immune activation. This review outlines the mechanistic foundations of DNAzyme catalysis

summarizes recent nanoengineering strategies that endow DNAzymes with programmable sensing and stimuli-responsive functions

and discusses how these systems bridge biosensing and catalytic immunometabolic functions. We conclude with perspectives on translational challenges and opportunities

endorsing programmable DNAzyme nanocatalysts as emerging preclinical platforms for biosensing-guided immunometabolic intervention.

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