Synthesis of Amphiphilic pH-Responsive Doxorubicin and Ferrocene-containing Copolyprodrug as Drug Self-delivery System and Its <italic style="font-style: italic">In Vitro</italic> Synergistic Apoptosis and Ferroptosis Tumor Therapy

Xiao-Mei Zhao; Peng Liu

doi:10.1007/s10118-025-3316-8

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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

RESEARCH ARTICLE | Updated：2025-07-14

- 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
- 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
- 高分子科学（英文） 2025年43卷第5期页码：730-737
- 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：
  
  Electronic supplementary information (ESI) is available free of charge in the online version of this article at http://doi.org/10.1007/s10118-025-3316-8.
- DOI：10.1007/s10118-025-3316-8
  中图分类号：
- 收稿：2024-12-27，
  
  修回：2025-01-22，
  
  录用：2025-02-06，
  
  网络首发：2025-03-13，
  
  纸质出版：2025-04-30
- Accepted：
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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, 730–737

Xiao-Mei Zhao, Peng Liu. 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[J]. Chinese Journal of Polymer Science, 2025, 43(5): 730-737. DOI: 10.1007/s10118-025-3316-8.
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, 730–737 DOI： 10.1007/s10118-025-3316-8.

Xiao-Mei Zhao, Peng Liu. 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[J]. Chinese Journal of Polymer Science, 2025, 43(5): 730-737. DOI: 10.1007/s10118-025-3316-8. DOI：

摘要

Amphiphilic pH-responsive copolyprodrug (P(ADH-DOX-Fc)-PEG) with doxorubicin and ferrocene as structural units in the main chain via acid-labile conjugations was designed as drug self-delivery system for combination of ferroptosis and chemotherapy in cancer treatment

exhibiting a combination index of 0.88.

Abstract

The diversity

complexity

heterogeneity

and drug resistance of tumors make it challenging to meet the clinical needs of a single apoptosis-inducing chemotherapy. The combination of apoptosis and ferroptosis is expected to address the side effects of chemotherapy and enhance therapeutic efficacy. Here

an amphiphilic pH-responsive doxorubicin (DOX) and ferrocene (Fc)-containing copolyprodrug (P(ADH-DOX-Fc)-PEG) was designed with high DOX and Fc content of 66.5% and 0.58 mmol/g by a facile polycondensation for combining chemotherapy with ferroptosis in cancer treatment. A drug self-delivery system (DSDS) with an average hydrodynamic diameter (

) of 135 nm can be easily obtained

via

self-assembly with the polyprodrug blocks as the hydrophobic core and PEG as the hydrophilic brush. The cumulative DOX release reached 72.7% in the simulated tumor intracellular acidic microenvironment within 56 h

whereas the premature drug leakage was only 6.2% in the simulated normal physiological medium. The 3-(4

5-dimethylthiazol-2-yl)-2

5-diphenyltetrazolium bromide (MTT) assay results indicated an IC

of 8.2 μg/mL

exhibiting enhanced anti-tumor efficacy and a successful combination of apoptosis and ferroptosis

with a combination index (CI) of 0.88.

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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

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

DOI：10.1007/s10118-025-3316-8

摘要

Abstract

关键词

Keywords

references