pH/Glutathione (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

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

RAPID COMMUNICATION | Updated：2025-07-26

- pH/Glutathione (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, Issue 8, Pages: 1277-1283(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：2025-03-11，
  
  Accepted：12 March 2025，
  
  Online First：15 May 2025，
  
  Published：01 August 2025
- Accepted：
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Yang, C.; Liu, P. pH/Glutathione (GSH) co-triggered degradable polyprodrug as drug self-delivery system for tumor-specific doxorubicin delivery: effect of aggregation states. Chinese J. Polym. Sci. 2025, 43, 1277–1283

Chen Yang, Peng Liu. pH/Glutathione (GSH) Co-triggered Degradable Polyprodrug as Drug Self-delivery System for Tumor-specific Doxorubicin Delivery: Effect of Aggregation States[J]. Chinese Journal of Polymer Science, 2025, 43(8): 1277-1283.
Yang, C.; Liu, P. pH/Glutathione (GSH) co-triggered degradable polyprodrug as drug self-delivery system for tumor-specific doxorubicin delivery: effect of aggregation states. Chinese J. Polym. Sci. 2025, 43, 1277–1283 DOI： 10.1007/s10118-025-3340-8.

Chen Yang, Peng Liu. pH/Glutathione (GSH) Co-triggered Degradable Polyprodrug as Drug Self-delivery System for Tumor-specific Doxorubicin Delivery: Effect of Aggregation States[J]. Chinese Journal of Polymer Science, 2025, 43(8): 1277-1283. DOI： 10.1007/s10118-025-3340-8.

摘要

The effect of the aggregation states of the pH/GSH co-triggered degradable polyprodrug on its tumor intracellular microenvironment (TME)-triggered drug release was investigated

by fabricating nanomedicines via fast precipitation and slow self-assembly. It is expected to be a secondary strategy for improved TME-responsive drug delivery in tumor chemotherapy

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

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/glutathione (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).

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references

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