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Fungus-targeted nanomicelles enable microRNA delivery for suppression of virulence in Aspergillus fumigatus as a novel antifungal approach

Summary

Researchers developed a new way to fight dangerous fungal infections caused by Aspergillus fumigatus by using tiny particles called nanomicelles to deliver genetic material (microRNAs) directly into fungal cells. These microRNAs target and reduce the production of melanin, a protective pigment that helps the fungus resist immune attacks. By weakening this defense, the fungal cells become more vulnerable to the body’s immune system and to stress, offering a novel approach to treat serious fungal infections that have become resistant to standard antifungal drugs.

Background

Aspergillus fumigatus causes invasive aspergillosis with high mortality rates and has developed resistance to azole antifungal agents. With only three main classes of antifungal drugs available, novel therapeutic strategies are urgently needed. MicroRNAs (miRNAs) represent a promising approach to regulate virulence factor expression in pathogenic fungi.

Objective

To develop a novel antifungal strategy using miRNA mimics targeting alb1, a gene involved in DHN-melanin synthesis (a virulence factor in A. fumigatus), and to deliver these miRNAs into fungal cells using fungus-targeted nanomicelles.

Results

miRNA introduction resulted in 2-fold reduction in alb1 expression and 1/3 reduction in Alb1 protein. Reduced melanin increased fungal susceptibility to hydrogen peroxide-induced oxidative stress by 20-25% and enhanced neutrophil-mediated killing by 58-59%. Dectin-1-installed micelles successfully delivered miRNAs into intact fungal cells, resulting in 50% reduction in CFUs after H2O2 exposure.

Conclusion

miRNAs can effectively regulate fungal virulence factors, and fungus-targeted nanomicelle delivery systems enable miRNA transport into intact fungal cells. This represents a novel therapeutic concept for controlling pathogenic fungal infections through virulence suppression rather than direct fungal killing.
  • Published in:Scientific Reports,
  • Study Type:Experimental Research,
  • Source: PMID: 40389718, DOI: 10.1038/s41598-025-02742-0
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