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

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.

Functionalizing Framework Nucleic‐Acid‐Based Nanostructures for Biomedical Application

“…Inspired by the excellent performance in intracellular transportation and the biocompatibility with living mammalian cells, we attempted to produce a novel tFNA-based delivery system in multiple types of microorganisms. In the field of antibacterial treatment, DNA tetrahedra have shown promising potential to serve as versatile assistants in terms of the stability, bacterial uptake, and inhibitory effect of antibacterial drugs, including antibiotics, antisense peptide nucleic acid (asPNA), [47] antibiotics, [115] antimicrobial peptides (AMPs), [116] antifungal histatin 5, [57] and antisense oligonucleotides (ASOs). [28] Initially, we constructed ampicillin-loaded tFNAs via a lowtemperature direct incubation method (4 °C for 24 h), followed using a 15 kDa size ultrafiltration centrifuge tube to separate any unincubated ampicillin molecules.…”

“…The tFNA/His‐5 complex showed enhanced uptake by Candida albicans and antifungal effects. [ 57 ] Furthermore, it has been illustrated that peptides have various binding mechanisms to DNA helices other than electrostatic forces, such as groove docking and hydrogen bonding. [ 58 ] The nature of DNA also endows various chemical modification approaches, such as fluorescence, crosslinking, and sorting/separation, which may boost both loading variety and capacity.…”

The Application of Small Molecules to the Control of Typical Species Associated With Oral Infectious Diseases

“…Drug delivery based tFNAs has been proposed and investigated broadly over the past years (Li et al, 2021;Zhang et al, 2022). Zhang et al synthesized tFNA/His-5, and by the modification of tFNAs, His-5 showed increased transport efficiency and improved anti-fungal effect (Zhang B et al, 2021). Moreover, Zhang et al also developed tFNAs with a controllable conformation as a delivery vehicle for antisense oligonucleotides, which provided a better platform for the applications of antisense antibacterial therapeutics (Zhang et al, 2018).…”

“…Zhang et al. synthesized tFNA/His-5, and by the modification of tFNAs, His-5 showed increased transport efficiency and improved anti-fungal effect ( Zhang B et al., 2021 ). Moreover, Zhang et al.…”

Histatin 5 Metallopeptides and Their Potential against Candida albicans Pathogenicity and Drug Resistance

“…In addition, reducing the size of the peptide to prevent protease attack and to decrease the cost of production is also an option. The use of efficient drug delivery systems, such as encapsulation in liposomes, for better stability and reduction of peptide toxicity, and use of tetrahedral DNA nanostructures, for their editability, biocompatibility and transportation efficiency as delivery vehicles, were also reported as a strategy to promote its use in therapy [67,87].…”