Tetrahedral DNA nanostructure improves transport efficiency and anti-fungal effect of histatin 5 against Candida albicans

Cell Prolif. 2021 May;54(5):e13020. doi: 10.1111/cpr.13020. Epub 2021 Mar 11.

Abstract

Objectives: Anti-microbial peptides (AMPs) have been comprehensively investigated as a novel alternative to traditional antibiotics against microorganisms. Meanwhile, Tetrahedral DNA nanostructures (TDNs) have gained attention in the field of biomedicine for their premium biological effects and transportation efficiency as delivery vehicles. Hence, in this study, TDN/Histatin 5 (His-5) was synthesized and the transport efficiency and anti-fungal effect were measured to evaluate the promotion of His-5 modified by TDNs.

Materials and methods: Tetrahedral DNA nanostructures/His-5 complex was prepared via electrostatic attraction and characterized by transmission electron microscopy (TEM), polyacrylamide gel electrophoresis (PAGE), dynamic light scattering (DLS) and electrophoretic light scattering (ELS). The anti-fungal effect of the TDN/His-5 complex was evaluated by determining the growth curve and colony-forming units of C. albicans. The morphological transformation of C. albicans was observed by light microscope and scanning electron microscope (SEM). Immunofluorescence was performed, and potassium efflux was detected to mechanistically demonstrate the efficacy of TDN/His-5.

Results: The results showed that Histatin 5 modified by TDNs had preferable stability in serum and was effectively transported into C. albicans, leading to the increased formation of intracellular reactive oxygen species, higher potassium efflux and enhanced anti-fungal effect against C. albicans.

Conclusions: Our study showed that TDN/His-5 was synthesized successfully. And by the modification of TDNs, His-5 showed increased transport efficiency and improved anti-fungal effect.

Keywords: Candida albicans; Fungi; Histatin 5; Tetrahedral framework nucleic acids; anti-microbial peptides.

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / metabolism
  • Antifungal Agents / pharmacology*
  • Candida albicans / drug effects*
  • DNA / chemistry*
  • Drug Stability
  • Histatins / chemistry*
  • Nanostructures / chemistry*
  • Nanostructures / toxicity
  • Potassium / metabolism
  • Reactive Oxygen Species / metabolism
  • Static Electricity

Substances

  • Antifungal Agents
  • Histatins
  • Reactive Oxygen Species
  • DNA
  • Potassium