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Phospholipid/protein co-mediated assembly of Cu2O nanoparticles for specific inhibition of growth and biofilm formation of pathogenic fungi

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  • ReceivedJun 9, 2020
  • AcceptedJul 6, 2020
  • PublishedOct 16, 2020

Abstract


Funded by

the National Natural Science Foundation of China(31870139,81873961)

the Natural Science Foundation of Tianjin(19JCZDJC33800)

the National Training Program of Innovation and Entrepreneurship for Undergraduates(201810055105)

and the Fundamental Research for the Central Universities.


Acknowledgment

This work was supported by the National Natural Science Foundation of China (31870139 and 81873961), the Natural Science Foundation of Tianjin (19JCZDJC33800), the National Training Program of Innovation and Entrepreneurship for Undergraduates (201810055105), and the Fundamental Research for the Central Universities.


Interest statement

The authors declare that they have no conflict of interest.


Contributions statement

Peng L, Wei H, and Yu Q designed and performed the experiments, and wrote the paper; Tian L and Xu J performed the data analysis; Yu Q and Li M supervised this study. All authors contributed to the general discussion and revision of the manuscript.


Author information

Liping Peng is currently a PhD student at the Department of Microbiology, College of Life Sciences, Nankai University. Her research focuses on the development of antimicrobial nanosystems for treatment of fungal/bacterial infections, together with investigation of the virulence factors of clinical pathogens.


Henan Wei is currently an undergraduate at the Department of Microbiology, College of Life Sciences, Nankai University. Her research focuses on the design of antifungal nanoplatforms for efficient anti-Candida therapy.


Qilin Yu received his PhD degree in 2013 from the College of Life Sciences, Nankai University. In 2017, he was appointed associated professor in Nankai University. In 2019, he started his visiting scholar research in Prof. Jeffrey Zink’s Lab, Department of Chemistry and Biochemistry, University of California, Los Angeles. His research interests focus on the design and application of nanotechnology-based self-assembly of biological systems.


Supplement

Supplementary information

Supporting data are available in the online version of the paper.


References

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  • Figure 1

    Characterizations of the synthesized Cu2O NPs and Cu2O-PE-BSA. (a) TEM images. (b) Zeta potential. (c) Size distribution. (d) FT-IR spectra.

  • Scheme 1

    (a) Illustration of construction of Cu2O-PE-BSA assembly and (b) the assembly-mediated inhibition of growth and biofilm formation of the pathogenic fungal cells.

  • Figure 2

    Pathogenic fungus-induced disassembly of the Cu2O-PE-BSA microaggregates. Note that the Cu2O-PE-BSA alone had aggregation with microparticle morphology (top), while the presence of the pathogenic C. albicans cells strongly adsorbed the particles and led to their disassembly (middle). The group of C. albicans alone (bottom) exhibited no autofluorescence on the surface.

  • Figure 3

    Fungal death and inhibition of hyphal growth by Cu2O NPs and Cu2O-PE-BSA. (a) Fungal death induced by Cu2O NPs and Cu2O-PE-BSA at different concentrations. (b) Percent of hyphal cells under treatment of the agents. (c) Microscopy images of the fungal cells under the hypha-inducing condition with 40 mg L−1 of the agents. * indicates significant difference between the control group (0) and the treated group (P < 0.05).

  • Figure 4

    Inhibition of fungal biofilm formation by Cu2O NPs and Cu2O-PE-BSA. (a) Confocal images of biofilms at different layers from the bottom to the top (0–40 μm). (b) Biomass of the fungal biofilms evaluated by XTT assays. (c) Expression of HWP1 in the treated biofilms revealed by Hwp1-GFP fluorescence quantification. * indicates significant difference between the control group (0) and the nanoparticle-treated group (P < 0.05).

  • Figure 5

    Impairment of mammalian cell viability by Cu2O NPs and Cu2O-PE-BSA. (a) Viability of 293T cells. (b) Viability of RAW264.7 cells. * indicates significant difference between the two groups (P < 0.05).

  • Figure 6

    Wound healing and reduction of fungal cells in the mouse wounds by Cu2O NPs and Cu2O-PE-BSA. (a) Illustration of the mouse skin wound model. (b) Wound healing rate of the treated mouse wounds. (c) Fungal burden in the wounds. * indicates significant difference between the groups (P < 0.05).

  • Table 1   IC50 of Cu2O NPs and Cu2O-PE-BSA against C. albicans growth and biofilm formation

    Strain

    IC50 against growth (mg L−1)

    IC50 against biofilm (mg L−1)

    Cu2O NPs

    Cu2O-PE-BSA

    Cu2O NPs

    Cu2O-PE-BSA

    SC5314

    < 20

    24.02

    34.21

    33.91

    BWP17

    < 20

    25.35

    < 20

    13.72

    NKFG1

    < 20

    20.16

    < 20

    18.67

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