Abstract

BackgroundMagnetic nanoparticles (MNPs) are characterized by unique physicochemical and biological properties that allow their employment as highly biocompatible drug carriers. Gelsolin (GSN) is a multifunctional actin-binding protein involved in cytoskeleton remodeling and free circulating actin sequestering. It was reported that a gelsolin derived phosphoinositide binding domain GSN 160–169, (PBP10 peptide) coupled with rhodamine B, exerts strong bactericidal activity.ResultsIn this study, we synthesized a new antibacterial and antifungal nanosystem composed of MNPs and a PBP10 peptide attached to the surface. The physicochemical properties of these nanosystems were analyzed by spectroscopy, calorimetry, electron microscopy, and X-ray studies. Using luminescence based techniques and a standard killing assay against representative strains of Gram-positive (Staphylococcus aureus MRSA Xen 30) and Gram-negative (Pseudomonas aeruginosa Xen 5) bacteria and against fungal cells (Candida spp.) we demonstrated that magnetic nanoparticles significantly enhance the effect of PBP10 peptides through a membrane-based mode of action, involving attachment and interaction with cell wall components, disruption of microbial membrane and increased uptake of peptide. Our results also indicate that treatment of both planktonic and biofilm forms of pathogens by PBP10-based nanosystems is more effective than therapy with either of these agents alone.ConclusionsThe results show that magnetic nanoparticles enhance the antimicrobial activity of the phosphoinositide-binding domain of gelsolin, modulate its mode of action and strengthen the idea of its employment for developing the new treatment methods of infections.

Highlights

  • In the past decade, surface modified magnetic nanoparticles composed of an iron oxide core and a metallic or polymeric shell have received attention as potential nanomaterials that might be used in theranostic applications, for example as drug transporters, inducers of magnetic

  • In this study we investigated the antimicrobial properties of gold and aminosilane coated magnetic nanoparticles in combination with derivatives of a PBP10 peptide including the native peptide (PBP10), a peptide with an additional amino acid, cysteine, functionalized by rhodamine B (Cys-PBP10-RhB) and a peptide functionalized by rhodamine B (PBP10-RhB)

  • Synthesis and physicochemical properties of peptide functionalized magnetic nanoparticles In this study peptide immobilization on the surface of magnetic nanoparticle was successfully performed in a one-pot process

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Summary

Introduction

The physicochemical properties of nanomaterials exert a strong impact on their biomedical applications and therapeutic properties. Such parameters as size, shape and surface charge determine nanoparticle stability and dispersity which in turn regulate biological effects and influence surface interactions, cellular uptake and delivery processes [10]. Nanoparticle surface chemistry partially defines their interaction with bioactive agents used during the functionalization process as well as their biological effects [11, 12]. It was reported that a gelsolin derived phosphoinositide binding domain GSN 160–169, (PBP10 peptide) coupled with rhodamine B, exerts strong bactericidal activity

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