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：2026-09-23

- Selective Antifungal Activity of Hyperbranched Polylysine Mediated by Charge-dependent Membrane Interactions
- Chinese Journal of Polymer Science Vol. 44, Issue 10, Pages: 3418-3436(2026)
- 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：
- DOI：10.1007/s10118-026-3721-7
  CLC：
- Received：26 March 2026，
  
  Accepted：20 April 2026，
  
  Online First：24 July 2026，
  
  Published：05 October 2026
- 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. 2026, 44, 3418–3436

Yi-Wei Wang, Jing-Hua Zhang, Ming Liu, et al. Selective Antifungal Activity of Hyperbranched Polylysine Mediated by Charge-dependent Membrane Interactions[J]. Chinese Journal of Polymer Science, 2026, 44(10): 3418-3436.
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. 2026, 44, 3418–3436 DOI： 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]. Chinese Journal of Polymer Science, 2026, 44(10): 3418-3436. DOI： 10.1007/s10118-026-3721-7.

摘要

This study introduces a hyperbranched polylysine

HPL2

which exerts its selective antifungal effect through membrane disruption

via

electrostatic interactions

shows excellent biocompatibility and minimal effects on the host gut microbiota.

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 potentia

l and appropriate hydrodynamic size

enabling HPL2 to penetrate through the fungal 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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