pH/GSH Co-triggered Degradable Polyprodrug as Drug Self-delivery System for Tumor-specific Doxorubicin Delivery: Effect of Aggregation States

Chen Yang; Peng Liu

doi:10.1007/s10118-025-3340-8

Your Location：

Home >

Browse articles >

pH/GSH Co-triggered Degradable Polyprodrug as Drug Self-delivery System for Tumor-specific Doxorubicin Delivery: Effect of Aggregation States

RAPID COMMUNICATION | Updated：2025-07-04

- pH/GSH Co-triggered Degradable Polyprodrug as Drug Self-delivery System for Tumor-specific Doxorubicin Delivery: Effect of Aggregation States
- Chinese Journal of Polymer Science Vol. 43, Pages: 1-7(2025)
- Affiliations：
  
  State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China
- Author bio：
  
  pliu@lzu.edu.cn
- Funds：
- DOI：10.1007/s10118-025-3340-8
  CLC：
- Received：09 February 2025，
  
  Revised：11 March 2025，
  
  Accepted：12 March 2025，
  
  Published Online：15 May 2025，
  
  Published：01 August 2025
- Accepted：
Scan QR Code
Yang, C.; Liu, P. pH/GSH co-triggered degradable polyprodrug as drug self-delivery system for tumor-specific doxorubicin delivery: effect of aggregation states. Chinese J. Polym. Sci. https://doi.org/10.1007/s10118-025-3340-8

Chen Yang, Peng Liu. pH/GSH Co-triggered Degradable Polyprodrug as Drug Self-delivery System for Tumor-specific Doxorubicin Delivery: Effect of Aggregation States[J/OL]. Chinese journal of polymer science, 2025, 431-7.
Yang, C.; Liu, P. pH/GSH co-triggered degradable polyprodrug as drug self-delivery system for tumor-specific doxorubicin delivery: effect of aggregation states. Chinese J. Polym. Sci. https://doi.org/10.1007/s10118-025-3340-8 DOI：

Chen Yang, Peng Liu. pH/GSH Co-triggered Degradable Polyprodrug as Drug Self-delivery System for Tumor-specific Doxorubicin Delivery: Effect of Aggregation States[J/OL]. Chinese journal of polymer science, 2025, 431-7. DOI： 10.1007/s10118-025-3340-8.

摘要

Abstract

Numerous efforts have been devoted to altering the dynamic covalent linkers between the drug structural units in polyprodrugs from the viewpoint of molecular structure; however

the effect of their aggregation states has not yet been explored. Here

the effect of aggregation states on the

in vitro

drug release and cytotoxicity was investigated using a pH/GSH co-triggered degradable doxorubicin (DOX)-based polyprodrug (PDOX) as a model

which was synthesized by the facile polymerization of a pH/GSH dual-triggered dimeric prodrug (DDOX

) and 2

2-dimethoxypropane (DMP) by forming acid-labile ketal bond. Owing to the pH/GSH dual-triggered disulfide/

-amide and acid-labile ketal linkers between the DOX structural units

the resultant PDOX exhibited excellent pH/GSH co-triggered DOX release. With a similar diameter

the PDOX-NPs1 nanomedicines

via

fast precipitation showed faster DOX release than PDOX-NPs2

via

slow self-assembly

regardless of their polymerization degree (DP). The effect of aggregation states is expected to be a secondary strategy for a more desired tumor intracellular microenvironment-responsive drug delivery for tumor chemotherapy

in addition to the molecular structures of polyprodrugs as drug self-delivery systems (DSDSs).

关键词

Keywords

references

Alex, J.; Weber, C.; Guerrero-Sanchez, C.; Schubert, U. S. Recent developments in synthetic approaches for macro molecular prodrugs. Prog. Polym. Sci. 2024 , 155 , 101855..

Girase, M. L.; Patil, P. G.; Ige, P. P. Polymer-drug conjugates as nanomedicine: a review. Int. J. Polym. Mater. Polym. Biomater. 2020 , 69 , 990−1014..

Qin, S. Y.; Zhang, A. Q.; Cheng, S. X.; Rong, L.; Zhang, X. Z. Drug self-delivery systems for cancer therapy. Biomaterials 2017 , 112 , 234−247..

Liu, P. Polyprodrugs for tumor chemotherapy: from molecular structure to drug release performance. J. Mater. Chem. B 2023 , 11 , 9565−9571..

Lin, C.; Liang, Y. X.; Guo, M. Y.; Saw, P. E.; Xu, X. D. Stimuli-responsive polyprodrug for cancer therapy. Mater. Today Adv. 2022 , 15 , 100266..

Li, X. M.; Liu, P. Synthesis and self-assembly of an acid/reduction co-triggered degradable amphiphilic copolyprodrug as a tumor-selective drug self-delivery system. J. Mater. Chem. B 2022 , 10 , 2926−2932..

Li, X.M.; Zhang, J.; Liu, P. Facile one-pot synthesis of amphiphilic acid/hypoxia co-triggered degradable diblock polyprodrug for tumor selective drug delivery. Int. J. Pharm. 2021 , 606 , 120941..

Li, J. G.; Liu, P. pH/Reduction dual-triggered degradable poly(doxorubicin) prodrug nanoparticles for leakage-free tumor-specific self-delivery. Macromol. Rapid Commun . 2018 , 39 , 1800381..

Yang, C.; Liu, P. Disulffde/ α -amide-bridged doxorubicin dimeric prodrug: effect of aggregation structures on pH/GSH dual-triggered drug release. Langmuir 2024 , 40 , 11098−11105..

Yang, C.; Liu, P. Regulating drug release performance of acid-triggered dimeric prodrug-based drug self-delivery system by altering its aggregation structure. Molecules 2024 , 29 , 3619..

Yang, C.; Liu, P. Structural aspects of dimeric prodrug-based carrier-free nanomedicines for tumor chemotherapy. J. Mater. Chem. B 2025 , 13 , 3292−3294..

Gillies, E. R.; Frechet, J. M. J. pH-Responsive copolymer assemblies for controlled release of doxorubicin. Bioconjugate Chem . 2005 , 16 , 361–368..

Missirlis, D.; Kawamura, R.; Tirelli, N.; Hubbell, J. A. Doxorubicin encapsulation and diffusional release from stable, polymeric, hydrogel nanoparticles. Eur. J. Pharm. Sci. 2006 , 29 , 120−129..

Zhang, P.; Li, J.; Ghazwani, M.; Zhao, W. C.; Huang, Y. X.; Zhang, X. L.; Venkataramanan, R.; Li, S. Effective co-delivery of doxorubicin and dasatinib usinga PEG-Fmoc nanocarrier for combination cancer chemotherapy. Biomaterials 2015 , 67 , 104−114..

Lee, J.; Kim, J.; Lee, Y. M.; Park, D.; Im, S.; Song, E. H.; Park, H.; Kim, W. J. Self-assembled nanocomplex between polymerized phenylboronic acid and doxorubicin for efficient tumor-targeted chemotherapy. Acta Pharm. Sin . 2017 , 38 , 848–858..

Li, J.; Yang, C.; Zhou, P. P.; Liu, P. Effect of aggregation structures of dimeric prodrug-based carrier-free nanomedicines for tumor chemotherapy. Colloid Surf. A-Physicochem. Eng. Aspects 2024 , 693 , 134044..

Wang, T.; Jin, M.; Chen, Z. L.; Hu, X. J.; Pu, L.; Pei, Z. C.; Pei, Y. X. Tumor microenvironment responsive supramolecular glyco-nanovesicles based on diselenium-bridged pillar[5 ] arene dimer for targeted chemotherapy. Chem. Commun. 2020 , 56 , 10642−10645..

Zhao, X. M.; Liu, P. Synthesis of amphiphilic pH-responsive doxorubicin and ferrocene-containing copolyprodrug as drug self-delivery system and its in vitro synergistic apoptosis and ferroptosis tumor therapy. Chinese J. Polym. Sci. 2025 , 43 , 10.1007/s10118−025-3316-8..

Huang, Y. K.; Tian, H.-R.; Zhang, M. Z.; He, J. L.; Liu, J.; Ni, P. H. Monoclonal antibody-conjugated polyphosphoester-hyd-DOX prodrug nanoparticles for targeted chemotherapy of liver cancer cells. Chinese J. Polym. Sci. 2021 , 39 , 1392−1402..

Views

Downloads

CSCD

Alert me when the article has been cited

Submit

Tools

Publicity Resources

Tumor-Penetrating and Mitochondria-Targeted Drug Delivery Overcomes Doxorubicin Resistance in Lung Cancer

Related Author

Xiao-Mei Zhao

Rui Dou

Meng-Xue Zhou

Jia-Yu Zhang

Xiao-Meng Cai

Li-Fo Ruan

Wen-Jiang Yang

Wen-Chu Lin

Related Institution

High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China, University of Science and Technology of China

Division of Nuclear Technology and Applications, Institute of High Energy Physics, Chinese Academy of Sciences (CAS)

Key Laboratory of Tea Biology and Resource Utilization of Ministry of Agriculture, Tea Research Institute, Chinese Academy of Agricultural Sciences

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics and University of Chinese Academy of Sciences (UCAS), Chinese Academy of Sciences (CAS)

School of Biomedical Engineering, Sun Yat-sen University

⁰