Azoreductase-Responsive Self-Assembled 10-Hydroxycamptothecin Nanofibers for Tumor-Specific Imaging and Therapy.

Authors

Li-Song Zhang, Tian-Hang Wang, Yu-Ying Wang, Hai-Yan Cui, Shi-Ting Weng, Chun Liu, Wen-Wen Zhao, Yi-Pan Zhu, Lu-Yuan Li, Zhi-Song Zhang

Published in

Biomacromolecules. Volume 27. Issue 11. Pages 7261-7273. Nov 09, 2026.

Abstract

Hypoxia is a defining feature of the tumor microenvironment (TME). The overexpression of azoreductase (AzoR) in hypoxic conditions enables it to serve as a trigger for drug release in tumor therapy. Developing a theranostic agent that is selectively activated in TME is vital for enhancing anti-tumor efficacy while minimizing side effects. Here, we designed and synthesized a supramolecular self-assembled nanofiber prodrug, NFK-(Azo)-HCPT, by conjugating a self-assembling peptide with the chemotherapeutic agent 10-hydroxycamptothecin (HCPT) via hypoxia-responsive azobenzene linkers. The prodrug exhibits excellent water solubility and forms supramolecular nanofibers through alkaline phosphatase (ALP)-catalyzed dephosphorylation. NFK-(Azo)-HCPT achieves significantly higher cellular uptake and tumor cell inhibition than HCPT alone. Its tumor targeting via the enhanced permeability and retention effects, showing selective activation and accumulation in tumors. NFK-(Azo)-HCPT reduced tumor size without altering bodyweight, validating its therapeutic potential. Collectively, the hypoxia-sensitive, enzyme-catalyzed self-assembly prodrug strategy offers a promising approach for precision oncology.

PMID:
43002007
Bibliographic data and abstract were imported from PubMed on 09 Nov 2026.

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