Tumor Microenvironment-responsive Self-immolative Polymers for Cancer Imaging and Therapy

Ihsan Ullah; Wen-Jun Yang; Ye Liu; Ci-Long Chu; Youyong Yuan

doi:10.1007/s10118-026-3633-6

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Tumor Microenvironment-responsive Self-immolative Polymers for Cancer Imaging and Therapy

REVIEW | Updated：2026-07-01

- Tumor Microenvironment-responsive Self-immolative Polymers for Cancer Imaging and Therapy
- Tumor Microenvironment-responsive Self-immolative Polymers for Cancer Imaging and Therapy
- Chinese Journal of Polymer Science 2026年44卷第7期页码：2112-2135
- Affiliations：
  
  a.School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou 511442, China
  b.National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, China
  c.Guangdong Province Key Laboratory of Biomedical Engineering, South China University of Technology, Guangzhou 510006, China
  d.Key Laboratory of Biomedical Materials of the Ministry of Education, South China University of Technology, Guangzhou 510006, China
- Author bio：
  
  yuanyy@scut.edu.cn
- Funds：
  
  This work was financially supported by the National Key R&D Program of China (No. 2024YFB3815100), the National Natural Science Foundation of China (Nos. 52373135 and 52573158), Guangdong Provincial Pearl River Talents Program (No. 2019QN01Y088), and Guangzhou Science and Technology Planning Project (No. 2025A04J7044).;Youyong Yuan received his Ph.D. degree in Polymer Chemistry and Physics from the University of Science and Technology of China in 2012. He subsequently conducted postdoctoral research in the Department of Biomedical Engineering at the National University of Singapore from 2012 to 2017. He joined the School of Biomedical Science and Engineering, South China University of Technology, in 2017, where he is currently a full Professor. He leads a research group focusing on biomaterials and drug delivery, bioorthogonal chemistry, and tumor microenvironment-responsive nanomedicine for precision cancer imaging and therapy.The authors declare no interest conflict.
- DOI：10.1007/s10118-026-3633-6
  中图分类号：
- 收稿：2026-01-26，
  
  修回：2026-02-23，
  
  录用：2026-02-24，
  
  网络首发：2026-05-14，
  
  纸质出版：2026-07-05
- Accepted：
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Ullah, I.; Yang, W. J.; Liu, Y.; Chu, C. L.; Yuan, Y. Tumor microenvironment-responsive self-immolative polymers for cancer imaging and therapy. Chinese J. Polym. Sci. 2026, 44, 2112–2135

Ihsan Ullah, Wen-Jun Yang, Ye Liu, et al. Tumor Microenvironment-responsive Self-immolative Polymers for Cancer Imaging and Therapy[J]. Chinese Journal of Polymer Science, 2026, 44(7): 2112-2135.
Ullah, I.; Yang, W. J.; Liu, Y.; Chu, C. L.; Yuan, Y. Tumor microenvironment-responsive self-immolative polymers for cancer imaging and therapy. Chinese J. Polym. Sci. 2026, 44, 2112–2135 DOI： 10.1007/s10118-026-3633-6.

Ihsan Ullah, Wen-Jun Yang, Ye Liu, et al. Tumor Microenvironment-responsive Self-immolative Polymers for Cancer Imaging and Therapy[J]. Chinese Journal of Polymer Science, 2026, 44(7): 2112-2135. DOI： 10.1007/s10118-026-3633-6.

摘要

Tumor microenvironment-responsive self-immolative polymers (SIPs) undergo cascade depolymerization triggered by pH

ROS

GSH

and enzymes. This amplified response enables enhanced tumor imaging

controlled drug release

and integrated theranostics

providing precise spatiotemporally regulated platforms for cancer diagnosis and combination therapy.

Abstract

Self-immolative polymers (SIPs) have recently emerged as a distinct class of stimuli-responsive materials that undergo programmed domino-like degradation in response to specific biochemical triggers. The unique biochemical characteristics of the tumor microenvironment (TME) include acidic pH

elevated glutathione (GSH) levels

excessive reactive oxygen species (ROS)

dysregulated enzymes

and hypoxia. TME-responsive SIPs have attracted significant attention for precise cancer imaging and therapy. By integrating labile linkages and modular structural design

these polymers can amplify weak biochemical signals into robust responses

enabling controlled drug release

signal amplification in imaging

and multifunctional theranostics. Compared with conventional responsive systems

SIP-based nanoplatforms offer enhanced sensitivity

tunable degradation kinetics

and the potential for sequential or cascade activation. In this review

we provide a comprehensive overview of the design principles

activation mechanisms

and functional applications of TME-responsive SIPs. We highlight representative strategies for their use in targeted drug delivery

tumor imaging

and synergistic therapeutic approaches and discuss the incorporation of emerging modalities such as near-infrared II (NIR-II) imaging and combination immunotherapy. Finally

we outline the major challenges and opportunities for advancing SIP-based nanomedicines for clinical translation and offer perspectives on how this rapidly evolving field may reshape the future of precision cancer diagnosis and treatment.

关键词

Keywords

references

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