Abstract

The combination of Fe3O4@Ag superparamagnetic hybrid nanoparticles and nitric oxide (NO) represents an innovative strategy for a localized NO delivery with a simultaneous antibacterial and antitumoral actions. Here, we report the design of Fe3O4@Ag hybrid nanoparticles, coated with a modified and nitrosated chitosan polymer, able to release NO in a biological medium. After their synthesis, physicochemical characterization confirmed the obtention of small NO-functionalized superparamagnetic Fe3O4@Ag NPs. Antibacterial assays demonstrated enhanced effects compared to control. Bacteriostatic effect against Gram-positive strains and bactericidal effect against E. coli were demonstrated. Moreover, NO-functionalized Fe3O4@Ag NPs demonstrated improved ability to reduce cancer cells viability and less cytotoxicity against non-tumoral cells compared to Fe3O4@Ag NPs. These effects were associated to the ability of these NPs act simultaneous as cytotoxic (necrosis inductors) and cytostatic compounds inducing S-phase cell cycle arrest. NPs also demonstrated low hemolysis ratio (<10%) at ideal work range, evidencing their potential for biomedical applications.Targeted and hemocompatible nitric oxide-releasing multi-functional hybrid nanoparticles for antitumor and antimicrobial applications.

Highlights

  • Since NPs can be functionalized with molecules of medical interest, in this work we proposed the synthesis of Fe3O4@Ag NPs that were further functionalized with thiolmodified chitosan (TCS), acting as a biocompatible layer, and enabling the insertion of nitric oxide (NO) moieties and their spontaneous release [20]

  • We synthesized Fe3O4 NPs by co-precipitation followed by the reduction of Ag+ by green tea extract on the surface of Fe3O4 NPs leading to the formation of Fe3O4@Ag NPs, as previous reported [23, 27]

  • The structure of the uncoated Fe3O4@Ag NPs was previously confirmed, evidencing the formation of a structure composed of 87% of Fe3O4 NPs and 13% of AgNPs through X-ray diffraction (XRD) analyses, which was maintained in Fe3O4@Ag/TCS NPs [23]

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Summary

Introduction

The use of nanoparticles (NPs) in biomedicine has been extensively reported in literature and continues to grow mostly due to their inherent physicochemical properties, the possibility of surface functionalization, in addition to antimicrobials and antitumoral properties [1]. In this regard, NP drug delivery systems lead to advantages over traditional drugs and their carrier systems, because the efficient delivery and release of the drug to the targeted location still requires improvement for the treatment of different diseases [2]. The research and development of efficient nanostructures are required for future advances in medical treatments [7]

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