Selective Antifungal Activity of Hyperbranched Polylysine Mediated by Charge-dependent Membrane Interactions

Yi-Wei Wang; Jing-Hua Zhang; Ming Liu; Ya-Dong Liu; Sheng-Xiang Ji

doi:10.1007/s10118-026-3721-7

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Selective Antifungal Activity of Hyperbranched Polylysine Mediated by Charge-dependent Membrane Interactions

RESEARCH ARTICLE | Updated：2026-07-25

- Selective Antifungal Activity of Hyperbranched Polylysine Mediated by Charge-dependent Membrane Interactions
- Selective Antifungal Activity of Hyperbranched Polylysine Mediated by Charge-dependent Membrane Interactions
- Chinese Journal of Polymer Science 2026年44卷页码：1-19
- Affiliations：
  
  a.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：
  
  sji@ciac.ac.cn
- Funds：
  
  This work was financially supported by the Jilin Province Science Technology Development Plan Project (No. 20230203144SF) and National Key Research and Development Program (Nos. 2022YFC2603500 and 2022YFC2603504).;The authors declare no interest conflict.Electronic supplementary information (ESI) is available free of charge in the online version of this article at http://doi.org/10.1007/s10118-026-3721-7.The data thatsupport the findings of this study are available from the corresponding author upon reasonable request.
- DOI：10.1007/s10118-026-3721-7
  中图分类号：
- 收稿：2026-03-26，
  
  录用：2026-04-20，
  
  网络首发：2026-07-24，
  
  纸质出版：2026-06
- Accepted：
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Wang, Y. W.; Zhang, J. H.; Liu, M.; Liu, Y. D.; Ji, S. X. Selective antifungal activity of hyperbranched polylysine mediated by charge-dependent membrane interactions. Chinese J. Polym. Sci. https://doi.org/10.1007/s10118-026-3721-7

Yi-Wei Wang, Jing-Hua Zhang, Ming Liu, et al. Selective Antifungal Activity of Hyperbranched Polylysine Mediated by Charge-dependent Membrane Interactions[J/OL]. Chinese Journal of Polymer Science, 2026, 441-19.
Wang, Y. W.; Zhang, J. H.; Liu, M.; Liu, Y. D.; Ji, S. X. Selective antifungal activity of hyperbranched polylysine mediated by charge-dependent membrane interactions. Chinese J. Polym. Sci. https://doi.org/10.1007/s10118-026-3721-7 DOI：

Yi-Wei Wang, Jing-Hua Zhang, Ming Liu, et al. Selective Antifungal Activity of Hyperbranched Polylysine Mediated by Charge-dependent Membrane Interactions[J/OL]. Chinese Journal of Polymer Science, 2026, 441-19. DOI： 10.1007/s10118-026-3721-7.

摘要

Abstract

Invasive fungal infections remain a significant global health threat

and the development of antifungal agents that selectively target fungi remains a critical challenge. This study investigates hyperbranched polylysine (HPL) with tunable molecular weight and charge density as a potential selective antifungal candidate. HPL1

with the lowest molecular weight

showed negligible antimicrobial activities

while HPL3

with the highest molecular weight

exhibited broad-spectrum antimicrobial effects against both bacteria and fungi. Notably

HPL2

the mediate molecular weight

demonstrated selective antifungal activities against clinically relevant

Candida

species

including

C. albicans

C. krusei

C. parapsilosis

C. tropicalis

and

C. glabrata

. This selectivity is mainly ascribed to its optimal zeta potential and appropriate hydrodynamic size

enabling HPL2 to penetrate through the f

ungal cell wall while stuck in bacterial cell envelopes. Mechanistic studies revealed that HPL2 initially adheres to the fungal surfaces induced

via

electrostatic interactions

then passively penetrates the fungal cell wall

disrupts membrane integrity

induces intracellular damage

and ultimately leads to cell death. Furthermore

HPL2 exhibited excellent biocompatibility and

in vivo

therapy efficacy with minimal disruption to host gut microbiota. These results highlight HPL2 as a promising antifungal agent with potent efficacy and favorable safety

which can be easily synthesized at kilogram scale.

关键词

Keywords

references

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