Ultrasound-induced Activation of Tetravalent Platinum Polyglutamate Nanoprodrug Accelerated by Coumarin Derivatives

Chao-Ying Kong; Chu-Wen Luo; Ya-Jun Xu; Na Shen; Zhao-Hui Tang

doi:10.1007/s10118-025-3469-5

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Ultrasound-induced Activation of Tetravalent Platinum Polyglutamate Nanoprodrug Accelerated by Coumarin Derivatives

RESEARCH ARTICLE | Updated：2026-01-13

- Ultrasound-induced Activation of Tetravalent Platinum Polyglutamate Nanoprodrug Accelerated by Coumarin Derivatives
- Ultrasound-induced Activation of Tetravalent Platinum Polyglutamate Nanoprodrug Accelerated by Coumarin Derivatives
- Chinese Journal of Polymer Science 2026年44卷第1期页码：44-56
- Affiliations：
  
  a.State Key Laboratory of Polymer Science and Technology, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
  b.School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
- Author bio：
  
  yjxu@ciac.ac.cn (Y.J.X.)
  ztang@ciac.ac.cn (Z.H.T.)
- Funds：
  
  This work was financially supported by the National Natural Science Foundation of China (Nos. 52533015, 52495013, 52403211, 52573183, 52273157, 52073279 and 52025035), Jilin Province, China (Nos. 20250601009RC and 20230508102RC), and Youth Innovation Promotion Association of the Chinese Academy of Sciences (No. 2022224).;Electronic supplementary information (ESI) is available free of charge in the online version of this article at http://doi.org/10.1007/s10118-025-3469-5.
- DOI：10.1007/s10118-025-3469-5
  中图分类号：
- 收稿：2025-08-29，
  
  录用：2025-09-30，
  
  网络出版：2025-12-25，
  
  纸质出版：2026-01-15
- Accepted：
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Kong, C. Y.; Luo, C. W.; Xu, Y. J.; Shen, N.; Tang, Z. H. Ultrasound-Induced activation of tetravalent platinum polyglutamate nanoprodrug accelerated by coumarin derivatives. Chinese J. Polym. Sci. 2026, 44, 44–56

Chao-Ying Kong, Chu-Wen Luo, Ya-Jun Xu, et al. Ultrasound-induced Activation of Tetravalent Platinum Polyglutamate Nanoprodrug Accelerated by Coumarin Derivatives[J]. Chinese Journal of Polymer Science, 2026, 44(1): 44-56.
Kong, C. Y.; Luo, C. W.; Xu, Y. J.; Shen, N.; Tang, Z. H. Ultrasound-Induced activation of tetravalent platinum polyglutamate nanoprodrug accelerated by coumarin derivatives. Chinese J. Polym. Sci. 2026, 44, 44–56 DOI： 10.1007/s10118-025-3469-5.

Chao-Ying Kong, Chu-Wen Luo, Ya-Jun Xu, et al. Ultrasound-induced Activation of Tetravalent Platinum Polyglutamate Nanoprodrug Accelerated by Coumarin Derivatives[J]. Chinese Journal of Polymer Science, 2026, 44(1): 44-56. DOI： 10.1007/s10118-025-3469-5.

摘要

Ultrasound (US)-triggered coumarin derivatives generate superoxide anion radicals (•O

−

)

reducing Pt(IV) prodrugs to cytotoxic Pt(II) drugs. A nanoprodrug (P-cisPt(IV)@5-MOP) co-delivered both agents

thus enabling dual-drug chemotherapy. It achieves 90.9% tumor inhibition

in vivo

with a 40% cure rate and low systemic toxicity

via

controllable activation.

Abstract

Given that platinum-based drugs are widely used clinically as chemotherapeutic agents

their severe toxic side effects have attracted significant attention. Consequently

the development of novel nanoprodrugs based on low-toxicity tetravalent platinum (Pt(IV)) complexes holds substantial research value. Herein

we discovered that coumarin derivatives exhibit inherent antitumor efficacy and significantly enhance superoxide anion radicals (•O

−

) generation in aqueous solutions under ultrasound (US) irradiation. Given that •O

−

is known to mediate the reducti

on of Pt(IV) to divalent platinum (Pt(II))

we engineered an US-responsive dual-drug nanoprodrug (P-cisPt(IV)@5-MOP). This nanoprodrug was prepared by covalently conjugating Pt(IV) and methoxy polyethylene glycol hydroxyl (mPEG-OH) to a poly(

-glutamic acid) (PLG) carrier

followed by encapsulating coumarin derivatives. Under low-intensity US irradiation (1.5 W/cm

1 MHz

10 min)

P-cisPt(IV)@5-MOP achieved a Pt(IV) reduction rate of 91.4%. Furthermore

upon US exposure

its half-maximal inhibitory concentration (IC

) against 4T1 breast cancer cells decreased dramatically from 25.7 μmol/L to 0.1 μmol/L. Remarkably

this system combined with US therapy yielded a tumor inhibition rate of 90.9%

with 40% of tumor-bearing mice achieving complete eradication of tumors

while exhibiting low systemic toxicity. Collectively

this work not only identifies a novel sonosensitizer capable of generating •O

−

but also develops a new class of ultrasound-activatable Pt(IV) nanoprodrug.

关键词

Keywords

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