Facile Synthesis of an Injectable Redox/pH Dual Stimuli-responsive Hydrogel System for Drug Release

Ning Duan; Xin-Ran Luo; Yan-Di Zhou; Jun-Yu Chai; Ji-Zhen Wang; Jing Gao; Hui-Fang Ye; Su-Yan Shan; Yong Liu; Chang-Chun Yu

doi:10.1007/s10118-026-3558-0

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Facile Synthesis of an Injectable Redox/pH Dual Stimuli-responsive Hydrogel System for Drug Release

RESEARCH ARTICLE | Updated：2026-03-26

- Facile Synthesis of an Injectable Redox/pH Dual Stimuli-responsive Hydrogel System for Drug Release
- Facile Synthesis of an Injectable Redox/pH Dual Stimuli-responsive Hydrogel System for Drug Release
- Chinese Journal of Polymer Science 2026年44卷第4期页码：1114-1125
- Affiliations：
  
  a.Laboratory of Novel Optoelectronic Technology for Ophthalmic Devices (NOTOD), School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University, Wenzhou 325027, China
  b.National Engineering Research Center of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China
  c.Department of vitreous and retinal center, Affiliated Eye Hospital of WenZhou Medical University, Hangzhou 310020, China
  d.Department of Ophthalmology the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
- Author bio：
  
  yongliu@wmu.edu.cn (Y.L.)
  changchun@wmu.edu.cn (C.C.Y.)
- Funds：
  
  This work was financially supported by the National Natural Science Foundation of China (Nos. 82502583 and U20A20338), Huadong Medicine Joint Funds of Natural Science Foundation of Zhejiang Province (No. LHDMY23H070004), and the Summit Advancement Disciplines of Zhejiang Province (Wenzhou Medical University-Pharmaceutics). We thank Prof. Zou Li (Tsinghua University) for his valuable suggestions. The valuable consultation and instrument supports from Scientific Research Centre of Wenzhou Medical University are also acknowledged.;The authors declare no interest conflict.The data supporting the findings of this study are available from the corresponding author upon reasonable request.
- DOI：10.1007/s10118-026-3558-0
  中图分类号：
- 收稿：2025-10-13，
  
  修回：2025-12-08，
  
  录用：2026-01-16，
  
  网络首发：2026-03-03，
  
  纸质出版：2026-04-05
- Accepted：
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Duan, N.; Luo, X. R.; Zhou, Y. D.; Chai, J. Y.; Wang, J. Z.; Gao, J.; Ye, H. F.; Shan, S. Y.; Liu, Y.; Yu, C. C. Facile synthesis of an injectable redox/pH dual stimuli-responsive hydrogel system for drug release. Chinese J. Polym. Sci. 2026, 44, 1114–1125

Ning Duan, Xin-Ran Luo, Yan-Di Zhou, et al. Facile Synthesis of an Injectable Redox/pH Dual Stimuli-responsive Hydrogel System for Drug Release[J]. Chinese Journal of Polymer Science, 2026, 44(4): 1114-1125.
Duan, N.; Luo, X. R.; Zhou, Y. D.; Chai, J. Y.; Wang, J. Z.; Gao, J.; Ye, H. F.; Shan, S. Y.; Liu, Y.; Yu, C. C. Facile synthesis of an injectable redox/pH dual stimuli-responsive hydrogel system for drug release. Chinese J. Polym. Sci. 2026, 44, 1114–1125 DOI： 10.1007/s10118-026-3558-0.

Ning Duan, Xin-Ran Luo, Yan-Di Zhou, et al. Facile Synthesis of an Injectable Redox/pH Dual Stimuli-responsive Hydrogel System for Drug Release[J]. Chinese Journal of Polymer Science, 2026, 44(4): 1114-1125. DOI： 10.1007/s10118-026-3558-0.

摘要

An injectable PEDOT@BEV hydrogel with dual redox/pH-responsiveness is developed for smart drug delivery. It shows rapid release under pathological cues of acidic/alkaline pH and ROS while remaining stable physiologically. It is effective in inhibiting angiogenesis

in vitro

and in corneal neovascularization model.

Abstract

Multiresponsive hydrogels

capable of responding to more than one external stimulus

have demonstrated great utility in biomedical applications. This study presents a facile method for preparing an injectable

dual redox/pH-responsive hydrogel system based on poly(3

4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) for the controlled delivery of pharmacologically active bevacizumab (BEV). The hydrogel system was fabricated

via

a one-step physical crosslinking process by mixing PEDOT:PSS with BEV

leveraging electrostatic interactions

hydrogen bonding

and ionic crosslinking. The resulting PEDOT@BEV system exhibited a homogeneously porous structure

robust mechanical stability

and good biocompatibility. Under acidic (pH=5) or alkaline (pH=10) conditions

especially when coupled with elevated reactive oxygen species (ROS) levels

the as-prepared PEDOT@BEV achieved rapid BEV release. This may be attributed to PEDOT oxidation and charge repulsion. In contrast

BEV release remained stable under physiological conditions (pH=7.4

0 mmol/L H

In vitro

results supported that the resulting PEDOT@BEV demonstrated potent anti-angiogenic efficacy

significantly inhibiting cellular migration and tube formation of human retinal vascular endothelial cells (HRVECs). The vascular endothelial growth factor expression was further reduced. In a mouse model of corneal neovascularization

the PEDOT@BEV system enabled the continuous controlled release of BEV for over 14 days. It exhibited superior anti-angiogenic efficacy compared to free BEV treatment

more effectively reducing neovascularization and corneal inflammation. The designed platform in this work demonstrated versatility by successfully incorporating other therapeutic antibodies (

e.g.

rituximab

trastuzumab)

highlighting its potential for ta

ilored drug delivery in oncology and neovascular diseases. The outcome of this study offers a promising strategy for spatiotemporally controlled drug release in response to specific microenvironmental cues.

关键词

Keywords

references

Cao, H.; Duan, L. X.; Zhang, Y.; Cao, J.; Zhang, K. Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity. Signal Transduct. Target. Ther. 2021 , 6 , 426..

Li, J.; Mooney, D. J. Designing hydrogels for controlled drug delivery. Nat. Rev. Mater. 2016 , 1 , 1..

Li, Z. Y.; Zhou, Y. Z.; Li, T. Y.; Zhang, J. J.; Tian, H. Stimuli-responsive hydrogels: fabrication and biomedical applications. View 2022 , 3 , 20200112..

Neumann, M.; di Marco, G.; Iudin, D.; Viola, M.; van Nostrum, C. F.; van Ravensteijn, B. G. P.; Vermonden, T. Stimuli-responsive hydrogels: the dynamic smart biomaterials of tomorrow. Macromolecules 2023 , 56 , 8377..

Wang, Y. Q.; Dou, X. Y.; Wang, H. F.; Wang, X.; Wu, D. C. Dendrimer-based hydrogels with controlled drug delivery property for tissue adhesion. Chinese J. Polym. Sci. 2021 , 39 , 1421−1430..

Yu, Y. B.; Cheng, Y.; Tong, J. Y.; Zhang, L.; Wei, Y.; Tian, M. Recent advances in thermo-sensitive hydrogels for drug delivery. J. Mater. Chem. 2021 , 9 , 2979..

Andrade, F.; Roca-Melendres, M. M.; Durán-Lara, E. F.; Rafael, D.; Schwartz, S. Jr. Stimuli-responsive hydrogels for cancer treatment: the role of pH, light, ionic strength and magnetic field. Cancers 2021 , 13 , 1164..

Monteiro, P. F.; Travanut, A.; Conte, C.; Alexander, C. Reduction-responsive polymers for drug delivery in cancer therapy—Is there anything new to discover. Wiley Interdiscip. Rev.: Nanomed. Nanobiotechnol. 2021 , 13 , e1678..

Yang, Z. Y.; Yin, J.; Xin, L.; Li, Y. F.; Huang, Y. J.; Yuan, R.; Zhou, Y. Research advancement of DNA-based intelligent hydrogels: manufacture, characteristics, application of disease diagnosis and treatment. Chin. Chem. Lett. 2024 , 35 , 109558..

Zhang, J.; Lin, Y. D.; Lin, Z.; Wei, Q.; Qian, J. Q.; Ruan, R. J.; Jiang, X. C.; Hou, L. X.; Song, J. B.; Ding, J. X.; Yang, H. H. Stimuli-responsive nanoparticles for controlled drug delivery in synergistic cancer immunotherapy. Adv. Sci. 2022 , 9 , 2103444..

Ovais, M.; Mukherjee, S.; Pramanik, A.; Das, D.; Mukherjee, A.; Raza, A.; Chen C. Y. Designing stimuli-responsive upconversion nanoparticles that exploit the tumor microenvironment. Adv. Mater. 2020 , 32 , 2000055..

Pan, Y. J.; Chen, Y. Y.; Wang, D. R.; Wei, C.; Guo, J.; Lu, D. R.; Chu, C. C.; Wang, C. C. Redox/pH dual stimuli-responsive biodegradable nanohydrogels with varying responses to dithiothreitol and glutathione for controlled drug release. Biomaterials 2012 , 33 , 6570..

Wang, Z.; Shi, J. J.; Gu, M. Y.; Zhang, X. J.; Sheng, R. L. A versatile strategy to construct surface functionalized pH/redox dual stimuli-responsive nanogels for targeted drug delivery. J. Appl. Polym. Sci. 2024 , 141 , e54908..

John, J. V.; Uthaman, S.; Augustine, R.; Chen, H.; Park, I. K.; Kim, I. pH/redox dual stimuli-responsive sheddable nanodaisies for efficient intracellular tumour-triggered drug delivery. J. Mater. Chem. B 2017 , 5 , 5027..

Pu, M. J.; Cao, H.; Zhang, H. J.; Wang, T. Y.; Li, Y. W.; Xiao, S. M.; Gu, Z. P. ROS-responsive h ydrogels: from design and additive manufacturing to biomedical applications. Mater. Horiz. 2024 , 11 , 3721..

Li, Y. C.; Tanigawa, R.; Okuzaki, H. Soft and flexible PEDOT/PSS films for applications to soft actuators. Smart Mater. Struct. 2014 , 23 , 074010..

Mochizuki, Y.; Horii, T.; Okuzaki, H. Effect of pH on structure and conductivity of PEDOT/PSS. Trans. Mat. Res. Soc. Japan 2012 , 37 , 307..

de Kok, M. M.; Buechel, M.; Vulto, S. I. E.; van den Weijer, P.; Meulenkamp, E. A.; de Winter, S. H. P. M.; Mank, A. J. G.; Vorstenbosch, H. J. M.; Weijtens, C. H. L.; van Elsbergen, V. Modification of PEDOT:PSS as hole injection layer in polymer LEDs. Physica Status Solid A. 2004 , 201 , 1342..

Enshaei, H.; Puiggalí-Jou, A.; Saperas, N.; Alemán, C. Conducting polymer nanoparticles for a voltage-controlled release of pharmacological chaperones. Soft Matter 2021 , 17 , 3314..

García-Fernández, A.; Lozano-Torres, B.; Blandez, J. F.; Monreal-Trigo, J.; Soto, J.; Collazos-Castro, J. E.; Alc añiz, M.; Marcos, M. D.; Sancenón, F.; Martínez-Máñez, R. Electro-responsive films containing voltage responsive gated mesoporous silica nanoparticles grafted onto PEDOT-based conducting polymer. J. Control. Rel. 2020 , 323 , 421..

He, G. Q.; Li, H.; Liu, J.; Hu, Y. L.; Liu, Y.; Wang, Z. L.; Jiang, P. Recent progress in implantable drug delivery systems. Adv. Mater. 2024 , 36 , 2312530..

Yuan, F.; Lin, D.; Zhang, Y.; Han, K.; Xu, Q.; Ma, H.; Huang, P. P.; Liu, Y.; Kong, L. D. Nanocomposite from alpha-tocopheryl succinate and chitosan-modified-graphene for efficient inhibition on choroidal melanoma via a chemotherapy-assisted-photothermal therapy. Chinese J. Polym. Sci. 2025 , 43 , 1387−1394..

Zhu, H. M.; Yu, J. W.; Ye, J. F.; Wu, Y. M.; Pan, J. T.; Li, Y. M.; Chen, C.; Zheng, L.; Liu, G.; Chu, C. C. Nanoparticle-mediated corneal neovascularization treatments: toward new generation of drug delivery systems. Chin. Chem. Lett. 2023 , 107648..

Li, M.; Chen, Z. F.; Liu, L.; Ma, X. Y.; Zou, J. Topical vitamin C promotes the recovery of corneal alkali burns in mice. J. Ophthalmol. 2021 , 2021 , 2406646..

Pal, S. C.; Das, M. C. Superprotonic conductivity of MOFs and other crystalline platforms beyond 10 −1 S cm −1 . Adv. Funct. Mater. 2021 , 31 , 2101584..

Yu, C. C.; Zhou, Y. D.; Yao, S.; Wang, Z. Y.; Ye, S. H.; Qi, R. B.; Hu, H.; Liu, K. K.; Wu, Y. B.; Lawson, T.; Yan, L.; Liu, Y.; Wu, W. W. A facile strategy to restore the optic nerve functionality using an injectable conducting hydrogel. Adv. Sci . 2025 , 2415601..

Wu, G.; Yu, C. F.; Wang, W. B.; Du, J. L.; Fu, Z. H.; Xu, G. L.; Li, M.; Wang, L. Mass spectrometry-based charge heterogeneity characterization of therapeutic mAbs with imaged capillary isoelectric focusing and ion-exchange chromatography as separation techniques. Anal. Chem. 2023 , 95 , 2548..

Pang, F. F.; Li, S.; Sun, W. Q.; Han, G. Z. Reversible conductivity modulation of PEDOT:PSS based on pH. Chem. Phys. 2017 , 186 , 246..

Guimard, N. K.; Gomez, N.; Schmidt, C. E. Conducting polymers in biomedical engineering. Polym. Sci. 2007 , 32 , 876..

Sousa, F.; Sarmento, B.; Neves-Petersen, M. T. Biophysical study of bevacizumab structure and bioactivity under thermal and pH-stresses. Acta Pharm. Nord. 2017 , 105 , 127..

Arvinte, T.; Palais, C.; Poirier, E.; Cudd, A.; Rajendran, S.; Brokx, S.; Dowd, J. Part 1: Physicochemical characterization of bevacizumab in undiluted 25 mg/mL drug product solutions: comparison of originator with a biosimilar candidate. J. Pharm. Biomed. Anal. 2019 , 175 , 112742..

Saini, N.; Lee, D. Y.; Yoon, M. H.; Awasthi, K. Unveiling the potential of Pt nanoparticle-decorated PEDOT:PSS membranes for efficient gas separation. ACS Appl. Mater. Interfaces. 2024 , 16 , 7700..

Heredia Rivera, U.; Kadian, S.; Nejati, S.; White, J.; Sedaghat, S.; Mutlu, Z.; Rahimi, R. Printed low-cost PEDOT: PSS/PVA polymer composite for radiation sterilization monitoring. ACS Sens. 2022 , 7 , 960..

Papadopoulos, N.; Martin, J.; Ruan, Q.; Rafique, A.; Rosconi, M. P.; Shi, E.; Pyles, E. A.; Yancopoulos, G. D.; Stahl, N.; Wiegand, S. J. Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranib izumab and bevacizumab. Angiogenesis 2012 , 15 , 171..

Garcia, J.; Hurwitz, H. I.; Sandler, A. B.; Miles, D.; Coleman, R. L.; Deurloo, R.; Chinot, O. L. Chinot. Bevacizumab (Avastin®) in cancer treatment: a review of 15 years of clinical experience and future outlook. Cancer Treat. Rev. 2020 , 86 , 102017..

Dos Reis, T. F.; de Castro, P. A.; Bastos, R. W.; Pinzan, C. F.; Souza, P. F. N.; Ackloo, S.; Hossain, M. A.; Drewry, D. H.; Alkhazraji, S.; Ibrahim, A. S.; Jo, H.; Lightfoot, J. D.; Adams, E. M.; Fuller, K. K.; deGrado, W. F.; Goldman, G. H. A host defense peptide mimetic, brilacidin, potentiates caspofungin antifungal activity against human pathogenic fungi. Nat. Commun. 2023 , 14 , 2052..

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