Multifunctional hybrid nanoplatform based on Fe3O4@Ag NPs for nitric oxide delivery: development, characterization, therapeutic efficacy, and hemocompatibility

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.

The Impact of Multiple Functional Layers in the Structure of Magnetic Nanoparticles and Their Influence on Albumin Interaction

“…The surface of the hybrid nanostructure Fe 3 O 4 @Ag NPs was functionalized with TCS, which can be further functionalized. Our previous publication reported the morphological and physicochemical characterizations of the NPs by different techniques [ 25 ]. Considering that both size and surface properties directly interfere with the functionality of NPs [ 26 , 27 ], the hydrodynamic diameters, polydispersity index values, and zeta potentials were measured to determine the influence of the surface of the three NPs on their properties.…”

Recent progress in the toxicity of nitric oxide-releasing nanomaterials

“…Polymer-coated metal or metal-oxide nanoparticles have also been reported as promising templates for delivering NO. 22,48,74 The surface functionalization enables the delivery of therapeutics, such as NO or traditional chemotherapeutics, and also promotes a targeted delivery to cancerous cells. 74,75 Among different nanoparticles, AuNPs have been one…”

“…22,48,74 The surface functionalization enables the delivery of therapeutics, such as NO or traditional chemotherapeutics, and also promotes a targeted delivery to cancerous cells. 74,75 Among different nanoparticles, AuNPs have been one…”

“…Much effort has been concentrated in the design of smart NO donors able to sensitively generate NO or NO-related species upon exogenous/endogenous stimuli at the desired site of application (tumor tissue), with minimum side effects to normal tissues. 3,74 Undoubtedly, nanotechnology has significantly contributed to the preparation of a variety of smart and efficient multifunctional NO-containing nanostructures in several biomedical applications, including cancer biology. Although several advances have been achieved in this topic, as presented in this work, some issues still need to be further explored: (i) in-depth mechanism of NO inducing cell death, and more importantly, cancer cell sensitization should be investigated by using genetic and molecular approaches, (ii) development of nanomedicines stable at room temperature and able to release NO in a controlled manner upon and external or internal stimuli, (iii) further studies (in vitro, in vivo and clinical) of multitherapy by combining NO donors and/or traditional chemotherapeutic drugs, and/or radiotherapy and/or X-ray are still strongly encouraged to be developed, (iv) strategies to enhance deep penetration of NO and/or chemotherapeutic drugs still need to the further developed, by considering the tumor microenvironment.…”

“…50 The apoptotic and necrotic effect of NO was also evident on osteosarcoma cells (MG63) when combined with a hybrid nanoparticle based on SPIONs and AgNPs 74. …”