Magnetite Nanoparticles Functionalized with Therapeutic Agents for Enhanced ENT Antimicrobial Properties.

In the context of inefficient antibiotics, antibacterial alternatives are urgently needed to stop the increasing resistance rates in pathogens. This study reports the fabrication and characterization of four promising magnetite-based antibiotic delivery systems for ENT (ear, nose and throat) applications. Magnetite nanoparticles were functionalized with streptomycin and neomycin and some were entrapped in polymeric spheres. The obtained nanomaterials are stable, with spherical morphology, their size ranging from ~2.8 to ~4.7 nm for antibiotic-coated magnetite nanoparticles, and from submicron sizes up to several microns for polymer-coated magnetite-antibiotic composites. Cell viability and antimicrobial tests demonstrated their biocompatibility on human diploid cells and their antibacterial effect against Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) opportunistic bacteria. The presence of the polymeric coat proved an enhancement in biocompatibility and a slight reduction in the antimicrobial efficiency of the spheres. Our results support the idea that functional NPs and polymeric microsystems containing functional NPs could be tailored to achieve more biocompatibility or more antimicrobial effect, depending on the bioactive compounds they incorporate and their intended application.

Novel Dextran Coated Cerium Doped Hydroxyapatite Thin Films.

Dextran coated cerium doped hydroxyapatite (Ca10-xCex(PO4)6(OH)2), with x = 0.05 (5CeHAp-D) and x = 0.1 (10CeHAp-D) were deposited on Si substrates by radio frequency magnetron sputtering technique for the first time. The morphology, composition, and structure of the resulting coatings were examined by scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDX), atomic force microscopy (AFM), metallographic microscopy (MM), Fourier transform infrared spectroscopy (FTIR), and glow discharge optical emission spectroscopy (GDOES), respectively. The obtained information on the surface morphologies, composition and structure was discussed. The surface morphologies of the CeHAp-D composite thin films are smooth with no granular structures. The constituent elements of the CeHAp-D target were identified. The results of the FTIR measurements highlighted the presence of peaks related to the presence of ν1, ν3, and ν4 vibration modes of (PO43-) groups from the hydroxyapatite (HAp) structure, together with those specific to the dextran structure. The biocompatibility assessment of 5CeHAp-D and 10CeHAp-D composite coatings was also discussed. The human cells maintained their specific elongated morphology after 24 h of incubation, which confirmed that the behavior of gingival fibroblasts and their proliferative capacity were not disturbed in the presence of 5CeHAp-D and 10CeHAp-D composite coatings. The 5CeHAp-D and 10CeHAp-D coatings' surfaces were harmless to the human gingival fibroblasts, proving good biocompatibility.

Could Iron-Nitrogen Doping Modulate the Cytotoxicity of TiO2 Nanoparticles?

Titanium dioxide nanoparticles (TiO2 NPs) are found in several products on the market that include paints, smart textiles, cosmetics and food products. Besides these, TiO2 NPs are intensively researched for their use in biomedicine, agriculture or installations to produce energy. Taking into account that several risks have been associated with the use of TiO2 NPs, our aim was to provide TiO2 NPs with improved qualities and lower toxicity to humans and the environment. Pure TiO2 P25 NPs and the same NPs co-doped with iron (1%) and nitrogen atoms (P25-Fe(1%)-N NPs) by hydrothermal treatment to increase the photocatalytic activity in the visible light spectrum were in vitro evaluated in the presence of human lung cells. After 24 and 72 h of incubation, the oxidative stress was initiated in a time- and dose-dependent manner with major differences between pure P25 and P25-Fe(1%)-N NPs as revealed by malondialdehyde and reactive oxygen species levels. Additionally, a lower dynamic of autophagic vacuoles formation was observed in cells exposed to Fe-N-doped P25 NPs compared to the pure ones. Therefore, our results suggest that Fe-N doping of TiO2 NPs can represent a valuable alternative to the conventional P25 Degussa particles in industrial and medical applications.

Anti-Biofilm Coatings Based on Chitosan and Lysozyme Functionalized Magnetite Nanoparticles.

Biofilms represent a common and increasingly challenging problem in healthcare practices worldwide, producing persistent and difficult to manage infections. Researchers have started developing antibiotic-free treatment alternatives in order to decrease the risk of resistant microbial strain selection and for the efficient management of antibiotic tolerant biofilm infections. The present study reports the fabrication and characterization of magnetite-based nanostructured coatings for producing biofilm-resistant surfaces. Specifically, magnetite nanoparticles (Fe3O4) were functionalized with chitosan (CS) and were blended with lysozyme (LyZ) and were deposited using the matrix-assisted pulsed laser evaporation (MAPLE) technique. A variety of characterization techniques were employed to investigate the physicochemical properties of both nanoparticles and nanocoatings. The biological characterization of the coatings assessed through cell viability and antimicrobial tests showed biocompatibility on osteoblasts as well as antiadhesive and antibiofilm activity against both Gram-negative and Gram-positive bacterial strains and no cytotoxic effect against human-cultured diploid cells.

Anti-Cancer Nanopowders and MAPLE-Fabricated Thin Films Based on SPIONs Surface Modified with Paclitaxel Loaded ß-Cyclodextrin.

Globally, cancer is the second most common cause of death, and Europe accounts for almost 25% of the global cancer burden, although its people make up only 10% of the world's population. Conventional systemically administered anti-cancer drugs come with important drawbacks such as inefficiency due to poor bioavailability and improper biodistribution, severe side effects associated with low therapeutic indices, and the development of multidrug resistance. Therefore, smart nano-engineered targeted drug-delivery systems with tailored pharmacokinetics and biodistribution which can selectively deliver anti-cancer agents directly to the tumor site are the solution to most difficulties encountered with conventional therapeutic tools. Here, we report on the synthesis, physicochemical characterization, and in vitro evaluation of biocompatibility and anti-tumor activity of novel magnetically targetable SPIONs based on magnetite (Fe3O4) nanoparticles' surface modified with ß-cyclodextrin (CD) and paclitaxel (PTX)-guest-host inclusion complexes (Fe3O4@ß-CD/PTX). Both pristine Fe3O4@ß-CD nanopowders and PTX-loaded thin films fabricated by MAPLE technique were investigated. Pristine Fe3O4@ß-CD and Fe3O4@ß-CD/PTX thin films were physicochemically characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), thermal analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The biocompatibility of bare magnetic nanocomposite thin films was evaluated by MTT cell viability assay on a normal 3T3 osteoblast cell line culture and by measuring the level of NO in the culture medium. No significant modifications, neither in cell viability nor in NO level, could be observed, thereby demonstrating the excellent biocompatibility of the SPIONs thin films. Inverted phase-contrast microscopy showed no evident adverse effect on the morphology of normal osteoblasts. On the other hand, Fe3O4@ß-CD/PTX films decreased the cell viability of the MG-63 osteosarcoma cell line by 85%, demonstrating excellent anti-tumor activity. The obtained results recommend these magnetic hybrid films as promising candidates for future delivery, and hyperthermia applications in cancer treatment.

Fe-N Co-Doped Titanium Dioxide Nanoparticles Induce Cell Death in Human Lung Fibroblasts in a p53-Independent Manner.

The advancement of nanotechnology in the last decade has developed an abundance of novel and intriguing TiO2-based nanomaterials that are widely used in many sectors, including industry (as a food additive and colorant in cosmetics, paints, plastics, and toothpaste) and biomedicine (photoelectrochemical biosensing, implant coatings, drug delivery, and new emerging antimicrobial agents). Therefore, the increased use of engineered nanomaterials in the industry has raised serious concern about human exposure and their unexpected cytotoxic effects. Since inhalation is considered the most relevant way of absorbing nanomaterials, different cell death mechanisms induced in MRC-5 lung fibroblasts, following the exposure to functionalized TiO2 NPs, were investigated. Long-term exposure to TiO2 nanoparticles co-doped with 1% of iron and nitrogen led to the alteration of p53 protein activity and the gene expression controlled by this suppressor (NF-kB and mdm2), DNA damage, cell cycle disruptions at the G2/M and S phases, and lysosomal membrane permeabilization and the subsequent release of cathepsin B, triggering the intrinsic pathway of apoptosis in a Bax- and p53-independent manner. Our results are of major significance, contributing to the understanding of the mechanisms underlying the interaction of these nanoparticles with in vitro biological systems, and also providing useful information for the development of new photocatalytic nanoparticles that are active in the visible spectrum, but with increased biocompatibility.

Bioactive Coatings Based on Hydroxyapatite, Kanamycin, and Growth Factor for Biofilm Modulation.

The occurrence of opportunistic local infections and improper integration of metallic implants results in severe health conditions. Protective and tunable coatings represent an attractive and challenging selection for improving the metallic devices' biofunctional performances to restore or replace bone tissue. Composite materials based on hydroxyapatite (HAp), Kanamycin (KAN), and fibroblast growth factor 2 (FGF2) are herein proposed as multifunctional coatings for hard tissue implants. The superior cytocompatibility of the obtained composite coatings was evidenced by performing proliferation and morphological assays on osteoblast cell cultures. The addition of FGF2 proved beneficial concerning the metabolic activity, adhesion, and spreading of cells. The KAN-embedded coatings exhibited significant inhibitory effects against bacterial biofilm development for at least two days, the results being superior in the case of Gram-positive pathogens. HAp-based coatings embedded with KAN and FGF2 protein are proposed as multifunctional materials with superior osseointegration potential and the ability to reduce device-associated infections.

Antioxidant and Anti-Inflammatory Properties of a Thuja occidentalis Mother Tincture for the Treatment of Ulcerative Colitis.

Inflammatory bowel disease (IBD) represents a group of chronic autoimmune and idiopathic disorders that are characteristic of industrialized countries. In contrast to drug therapies, which exert several side effects, herbal remedies have constantly attracted the attention of researchers. Therefore, in the present study, a mother tincture (MT) from fresh, young, non-woody Thuja occidentalis L. branches with leaves was obtained using distillation-based techniques. Further, this was used to assess its in vitro and in vivo antioxidant activities and anti-inflammatory properties, and to validate it as a potential phytotherapeutic treatment for IBD. The characterization of the tincture included common phytochemical screening assays for antioxidant capacity measurement, cell viability assays on Caco-2 colon cells, and in vivo assessment of antioxidant and anti-inflammatory effects by histopathological and ultrastructural analysis of the intestinal mucosa, measurement of reduced glutathione, lipid peroxidation, and gene expression of the inflammation markers (interleukin-6 and tumor necrosis factor-α) in intestine after oral administration to an experimental mouse model of colon inflammation (colitis) developed by intrarectal administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Our study proved that administration of 25 or 50 mg T. occidentalis MT/kg of body weight/day by gavage for 7 days succeeded in inhibiting the inflammatory process induced by TNBS in the intestine, most probably because of its rich contents of flavonoids and phenolic compounds. These data could contribute to the formulation of therapeutic products based on T. occidentalis that could come to the aid of IBD patients.

Development and Biocompatibility Evaluation of Photocatalytic TiO2/Reduced Graphene Oxide-Based Nanoparticles Designed for Self-Cleaning Purposes.

Graphene is widely used in nanotechnologies to amplify the photocatalytic activity of TiO2, but the development of TiO2/graphene composites imposes the assessment of their risk to human and environmental health. Therefore, reduced graphene oxide was decorated with two types of TiO2 particles co-doped with 1% iron and nitrogen, one of them being obtained by a simultaneous precipitation of Ti3+ and Fe3+ ions to achieve their uniform distribution, and the other one after a sequential precipitation of these two cations for a higher concentration of iron on the surface. Physico-chemical characterization, photocatalytic efficiency evaluation, antimicrobial analysis and biocompatibility assessment were performed for these TiO2-based composites. The best photocatalytic efficiency was found for the sample with iron atoms localized at the sample surface. A very good anti-inhibitory activity was obtained for both samples against biofilms of Gram-positive and Gram-negative strains. Exposure of human skin and lung fibroblasts to photocatalysts did not significantly affect cell viability, but analysis of oxidative stress showed increased levels of carbonyl groups and advanced oxidation protein products for both cell lines after 48 h of incubation. Our findings are of major importance by providing useful knowledge for future photocatalytic self-cleaning and biomedical applications of graphene-based materials.

Interaction of New-Developed TiO2-Based Photocatalytic Nanoparticles with Pathogenic Microorganisms and Human Dermal and Pulmonary Fibroblasts.

TiO2-based photocatalysts were obtained during previous years in order to limit pollution and to ease human daily living conditions due to their special properties. However, obtaining biocompatible photocatalysts is still a key problem, and the mechanism of their toxicity recently received increased attention. Two types of TiO2 nanoparticles co-doped with 1% of iron and nitrogen (TiO2-1% Fe-N) atoms were synthesized in hydrothermal conditions at pH of 8.5 (HT1) and 5.5 (HT2), and their antimicrobial activity and cytotoxic effects exerted on human pulmonary and dermal fibroblasts were assessed. These particles exhibited significant microbicidal and anti-biofilm activity, suggesting their potential application for microbial decontamination of different environments. In addition, our results demonstrated the biocompatibility of TiO2-1% Fe-N nanoparticles at low doses on lung and dermal cells, which may initiate oxidative stress through dose accumulation. Although no significant changes were observed between the two tested photocatalysts, the biological response was cell type specific and time- and dose-dependent; the lung cells proved to be more sensitive to nanoparticle exposure. Taken together, these experimental data provide useful information for future photocatalytic applications in the industrial, food, pharmaceutical, and medical fields.

Innovative Self-Cleaning and Biocompatible Polyester Textiles Nano-Decorated with Fe-N-Doped Titanium Dioxide.

The development of innovative technologies to modify natural textiles holds an important impact for medical applications, including the prevention of contamination with microorganisms, particularly in the hospital environment. In our study, Fe and N co-doped TiO2 nanoparticles have been obtained via the hydrothermal route, at moderate temperature, followed by short thermal annealing at 400 °C. These particles were used to impregnate polyester (PES) materials which have been evaluated for their morphology, photocatalytic performance, antimicrobial activity against bacterial reference strains, and in vitro biocompatibility on human skin fibroblasts. Microscopic examination and quantitative assays have been used to evaluate the cellular morphology and viability, cell membrane integrity, and inflammatory response. All treated PES materials specifically inhibited the growth of Gram-negative bacilli strains after 15 min of contact, being particularly active against Pseudomonas aeruginosa. PES fabrics treated with photocatalysts did not affect cell membrane integrity nor induce inflammatory processes, proving good biocompatibility. These results demonstrate that the treatment of PES materials with TiO2-1% Fe-N particles could provide novel biocompatible fabrics with short term protection against microbial colonization, demonstrating their potential for the development of innovative textiles that could be used in biomedical applications for preventing patients' accidental contamination with microorganisms from the hospital environment.

Photocatalytic, Antimicrobial and Biocompatibility Features of Cotton Knit Coated with Fe-N-Doped Titanium Dioxide Nanoparticles.

Our research was focused on the evaluation of the photocatalytic and antimicrobial properties, as well as biocompatibility of cotton fabrics coated with fresh and reused dispersions of nanoscaled TiO2-1% Fe-N particles prepared by the hydrothermal method and post-annealed at 400 °C. The powders were characterized by X-ray diffraction (XRD), Mössbauer spectroscopy and X-ray photoelectron spectroscopy. The textiles coated with doped TiO2 were characterized by scanning electron microscopy and energy dispersive X-ray analyses, and their photocatalytic effect by trichromatic coordinates of the materials stained with methylene blue and coffee and exposed to UV, visible and solar light. The resulting doped TiO2 consists of a mixture of prevailing anatase phase and a small amount (~15%-20%) of brookite, containing Fe3+ and nitrogen. By reusing dispersions of TiO2-1% Fe-N, high amounts of photocatalysts were deposited on the fabrics, and the photocatalytic activity was improved, especially under visible light. The treated fabrics exhibited specific antimicrobial features, which were dependent on their composition, microbial strain and incubation time. The in vitro biocompatibility evaluation on CCD-1070Sk dermal fibroblasts confirmed the absence of cytotoxicity after short-term exposure. These results highlight the potential of TiO2-1% Fe-N nanoparticles for further use in the development of innovative self-cleaning and antimicrobial photocatalytic cotton textiles. However, further studies are required in order to assess the long-term skin exposure effects and the possible particle release due to wearing.