Nanoarchitectonics for synergistic activity of multimetallic nanohybrids as a possible approach for antimicrobial resistance (AMR).

The global threat posed by antimicrobial resistance (AMR) to public health is an immensurable problem. The effectiveness of treating infections would be more at risk in the absence of effective antimicrobials. Researchers have shown an amplified interest in alternatives, such as developing advanced metallic nanohybrids as new therapeutic candidates for antibiotics due to their promising effectiveness against resistant microorganisms. In recent decades, the antimicrobial activity of monometallic nanoparticles has received extensive study and solid proof, providing new opportunities for developing multimetallic nanohybrid antimicrobials. Advanced metallic nanohybrids are an emerging remedy for a number of issues that develop in the field of medicine. Advanced metallic nanohybrids have shown a promising ability to combat resistant microorganisms due to their overall synergistic activity. Formulating advanced multimetallic nanohybrids falling under the umbrella of the growing field of nanoarchitectonics, which extends beyond nanotechnology. The underlying theory of nanoarchitectonics involves utilizing nanoscale units that follow the concepts of nanotechnology to architect nanomaterials. This review focuses on a comprehensive description of antimicrobial mechanisms of metallic nanohybrids and their enabling future insights on the research directions of developing the nanoarchitectonics of advanced multimetallic nanohybrids as novel antibiotics through their synergistic activity.

Potential antifungal applications of heterometallic silica nanohybrids: A synergistic activity.

An estimated 1.7 million fatalities and 150 million cases worldwide are attributed to fungal infections annually, that are in rise due to immunocompromised patient population. The challenges posed by traditional treatments can be addressed with the help of nanotechnology advancements. In this study, Co, Cu, and Ag-were doped into silica nanoparticles. Then the synthesized monometallic silica nanohybrids were combined to formulate heterometallic silica nanohybrids, characterized structurally and morphologically, compared, and evaluated for antifungal activity based on their individual and synergistic activity. The antifungal assays were conducted by using ATCC cultures of Candida albicans and QC samples of Trichophyton rubrum, Microsporum gypseum, and Aspergillus niger. The MIC (ranging from 49.00 to 1560.00 µg/mL), MFC (ranging from 197.00 to 3125.00 µg/mL), IC50 values (ranging from 31.10 to 400.80 µg/mL), and FICI of nanohybrids were determined and compared. Moreover, well diffusion assay was performed. ABTS assay and DPPH assay were conducted to investigate the radical scavenging activity (RSA) of nanohybrids. SEM analysis clearly evidenced the structural deformations of each fungal cells and spores due to the treatment with trimetallic nanohybrid. According to the results, the trimetallic silica nanohybrids exhibited the most powerful synergistic RSA and the most effective antifungal activity, compared to the bimetallic silica nanohybrids.

Preparation and characterization of Fe-ZnO cellulose-based nanofiber mats with self-sterilizing photocatalytic activity to enhance antibacterial applications under visible light.

Bacterial infections and antibiotic resistance have posed a severe threat to public health in recent years. One emerging and promising approach to this issue is the photocatalytic sterilization of nanohybrids. By utilizing ZnO photocatalytic sterilization, the drawbacks of conventional antibacterial treatments can be efficiently addressed. This study examines the enhanced photocatalytic sterilizing effectiveness of Fe-doped ZnO nanoparticles (Fe-ZnO nanohybrids) incorporated into polymer membranes that are active in visible light. Using the co-precipitation procedure, Fe-ZnO nanohybrids (Fe x Zn100-x O) have been generated using a range of dopant ratios (x = 0, 3, 5, 7, and 10) and characterized. The ability to scavenge free radicals was assessed and the IC50 value was calculated using the DPPH test at different catalytic concentrations. PXRD patterns showed a hexagonal wurtzite structure, which indicated that the particle size of the nanohybrid decreased as the dopant concentration rose. It was demonstrated by UV-vis diffuse reflectance experiments that the band gap of the nanohybrid decreased (redshifted) with Fe doping. The photocatalytic activity under sunlight increased steadily to 87% after Fe was added as a dopant. The Fe 5%-ZnO nanohybrid exhibited the lowest IC50 value of 81.44 µg mL-1 compared to ZnO, indicating the highest radical scavenging activity and the best antimicrobial activity. The Fe 5%-ZnO nanohybrid, which is proven to have the best photocatalytic sterilization activity, was then incorporated into a cellulose acetate polymer membrane by electrospinning. Disc diffusion assay confirmed the highest antimicrobial activity of the Fe 5%-ZnO nanohybrid incorporated electrospun membrane against Staphylococcus aureus (ATCC 25923), Streptococcus pneumoniae (ATCC 49619), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), and Candida albicans (ATCC 10231) under visible light. As a result, Fe 5%-ZnO nanofiber membranes have the potential to be employed as self-sterilizing materials in healthcare settings.

Ilmenite-Grafted Graphene Oxide as an Antimicrobial Coating for Fruit Peels.

Postharvest loss is a significant global challenge that needs to be urgently addressed to sustain food systems. This study describes a simple microwave-assisted green synthesis method in developing a nanohybrid material combining natural ilmenite (FeTiO3) and graphene oxide (GO) as a promising antimicrobial fruit peel coating to reduce postharvest loss. The natural ilmenite was calcined in an inert environment and was mixed with GO in a microwave reactor to obtain the nanohybrid. The nanohybrid was then incorporated into an alginate biopolymer to form the fruit coating. Microscopic images revealed successful grafting of FeTiO3 nanoparticles onto the GO sheets. Spectroscopic measurements of Raman, X-ray photoemission, and infrared provided insights into the interactions between the two matrices. The optical band gap calculated from Tauc's relation using UV-vis data showed a significant reduction in the band gap of the hybrid compared to that of natural ilmenite. The antimicrobial activity was assessed using Escherichia coli, which showed a substantial decrease in colony counts. Bananas coated with the nanohybrid showed a doubling in the shelf life compared with uncoated fruits. Consistent with this, the electronic nose (E-nose) measurements and freshness indicator tests revealed less deterioration of the physicochemical properties of the coated bananas. Overall, the results show promising applications for the ilmenite-grafted GO nanohybrid as a food coating capable of minimizing food spoilage due to microbial activity.

Sustainable Synthesis of Highly Functionalized Activated Carbon using Plasma Technology.

Surface functionalized activated carbon (SFAC) has been used for several applications, including adsorption, catalysis and energy storage materials. Existing chemical and physical activation methods for surface functionalization are mostly identified as expensive, inefficient, and non-green methods. Plasma, known as the fourth state of matter, has recently been recognized as an attractive and sustainable method for introducing a higher degree of surface functionality to activated carbon. It also improves the bulk chemical structure and the properties of SFAC. The surface functionalization process is governed by discharge gas, discharge source, discharge efficiency and discharge time. The majority of researchers have utilized oxygen plasma as the discharge gas. However, ammonia, carbon dioxide, atmospheric air, specific gases such as chlorine and hydrogen sulfide, and neutral gases such as nitrogen and argon have also been used as the discharge gas. These plasma activations were conducted under different power conditions (W to kW) and varying treatment times (seconds to hours) using different plasma sources such as dielectric barrier discharge (DBD), arc, radio frequency (RF) and microwave (MW) for the surface functionalization. Most of the researchers have experienced both positive and negative co-relationships between principal parameters and surface functional groups (SFGs), surface area, porosity and other surface features such as roughness and hydrophilicity. However, a comprehensive review on the effects of these parameters on the final material properties is lacking. Therefore, this Review focuses on the recent developments in the utilization of plasma as a surface activation technique for activated carbon. Furthermore, an in-depth analysis of the relationship between experimental parameters and the resultant surface features of activated carbon is carried out and discussed. The functionalization mechanisms related to plasma activation have also been illustrated. The aging effect, which negatively impacts surface functionalized activated carbon, is also emphasized. Finally, the recent advances in applications of SFAC, challenges and future perspectives are discussed in detail.

A comprehensive review on electrospun nanohybrid membranes for wastewater treatment.

Electrospinning, being a versatile and straightforward method to produce nanofiber membranes, has shown significant advancement in recent years. On account of the unique properties such as high surface area, high porosity, mechanical strength, and controllable surface morphologies, electrospun nanofiber membranes have been found to have a great potential in many disciplines. Pure electrospun fiber mats modified with different techniques of surface modification and additive incorporation have exhibited enhanced properties compared to traditional membranes and are even better than the as-prepared electrospun membranes. In this review, we have summarized recently developed electrospun nanohybrids fabricated by the incorporation of functional specific nanosized additives to be used in various water remediation membrane techniques. The adsorption, filtration, photocatalytic, and bactericidal capabilities of the hybrid membranes in removing common major water pollutants such as metal ions, dyes, oils, and biological pollutants have been discussed. Finally, an outlook on the future research pathways to fill the gaps existing in water remediation have been suggested.

A Novel Green Approach to Synthesize Curcuminoid-Layered Double Hydroxide Nanohybrids: Adroit Biomaterials for Future Antimicrobial Applications.

Thermal instability, photodegradation, and poor bioavailability of natural active ingredients are major drawbacks in developing effective natural product-based antimicrobial formulations. These inherited issues could be fruitfully mitigated by the introduction of natural active ingredients into various nanostructures. This study focuses on the development of a novel green mechanochemical synthetic route to incorporate curcuminoids into Mg-Al-layered double hydroxides. The developed one-pot and scalable synthetic approach makes lengthy synthesis procedures using toxic solvents redundant, leading to improved energy efficiency. The hydrotalcite-shaped nanohybrids consist of surface and interlayer curcuminoids that have formed weak bonds with layered double hydroxides as corroborated by X-ray diffractograms, X-ray photoelectron spectra, and Fourier transmission infrared spectra. The structural and morphological properties resulted in increased thermal stability of curcuminoids. Slow and sustained release of the curcuminoids was observed at pH 5.5 for a prolonged time up to 7 h. The developed nanohybrids exhibited zeroth-order kinetics, favoring transdermal application. Furthermore, the efficacy of curcuminoid incorporated LDHs (CC-LDH) as an anticolonization agent was investigated against four wound biofilm-forming pathogens, Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant Staphyloccocus aureus, and Candida albicans, using a broth dilution method and an in vitro biofilm model system. Microbiological studies revealed a 54-58% reduction in biofilm formation ability of bacterial pathogens in developed nanohybrids compared to pure curcuminoids. Therefore, the suitability of these green-chemically synthesized CC-LDH nanohybrids for next-generation antimicrobial applications with advanced dermatological/medical properties is well established.

Facile Mechanochemical Approach To Synthesizing Edible Food Preservation Coatings Based On Alginate/Ascorbic Acid-Layered Double Hydroxide Bio-Nanohybrids.

A bionanohybrid based on ascorbic acid-intercalated layered double hydroxides (LDHs) was synthesized using a facile and novel mechanochemical grinding technique, and its efficacy as an edible food coating is reported. Ascorbic acid-intercalated Mg-Al-LDHs (AA-LDHs) are synthesized using a green water-assisted grinding approach. The successful synthesis of the mechanochemically ground AA-LDHs was confirmed by the shifts observed in the basal peaks of the LDHs based on a powder X-ray diffraction, changes in the positions of vibrational frequencies of ascorbic acid based on Fourier Transform Infrared Spectroscopy, and significant changes in the intensity and peak positions of the core-shell bands based on X-ray photoelectron spectroscopy. The resulting nanohybrid further demonstrates thermal stability in thermogravimetric and derivative thermogravimetric analysis. Transmission electron microscopy images of the mechanochemically synthesized AA-LDHs reveal a plate-like morphology, which is a characteristic of the hydrotalcite-like structure. In a novel application, an edible coating was prepared by blending the AA-LDHs into a biocompatible alginate matrix, and the coating was developed on freshly plucked strawberries using the dip-coating method. In order to evaluate the efficacy of the coating, the total phenolic content, pH, microbial growth, weight loss, titratable acidity, and ascorbic acid content were monitored in the coated and uncoated fruits for a period of 18 days. The results reveal that the shelf life of strawberries increases from 9 days to 15 days for the nanohybrid coated fruits, suggesting the potential food preservation applications of the nanohybrid.

Characterization of different bubble formulations for blood-brain barrier opening using a focused ultrasound system with acoustic feedback control.

Focused ultrasound combined with bubble-based agents serves as a non-invasive way to open the blood-brain barrier (BBB). Passive acoustic detection was well studied recently to monitor the acoustic emissions induced by the bubbles under ultrasound energy, but the ability to perform reliable BBB opening with a real-time feedback control algorithm has not been fully evaluated. This study focuses on characterizing the acoustic emissions of different types of bubbles: Optison, Definity, and a custom-made nanobubble. Their performance on reliable BBB opening under real-time feedback control based on acoustic detection was evaluated both in-vitro and in-vivo. The experiments were conducted using a 0.5 MHz focused ultrasound transducer with in-vivo focal pressure ranges from 0.1-0.7 MPa. Successful feedback control was achieved with all three agents when combining with infusion injection. Localized opening was confirmed with Evans blue dye leakage. Microscopic images were acquired to review the opening effects. Under similar total gas volume, nanobubble showed a more reliable opening effect compared to Optison and Definity (p < 0.05). The conclusions obtained from this study confirm the possibilities of performing stable opening using a feedback control algorithm combined with infusion injection. It also opens another potential research area of BBB opening using sub-micron bubbles.

Temperature-sensitive liposomal ciprofloxacin for the treatment of biofilm on infected metal implants using alternating magnetic fields.

Implants are commonly used as a replacement for damaged tissue. Many implants, such as pacemakers, chronic electrode implants, bone screws, and prosthetic joints, are made of or contain metal. Infections are one of the difficult to treat complications associated with metal implants due to the formation of biofilm, a thick aggregate of extracellular polymeric substances (EPS) produced by the bacteria. In this study, we treated a metal prosthesis infection model using a combination of ciprofloxacin-loaded temperature-sensitive liposomes (TSL) and alternating magnetic fields (AMF). AMF heating is used to disrupt the biofilm and release the ciprofloxacin-loaded TSL. The three main objectives of this study were to (1) investigate low- and high-temperature-sensitive liposomes (LTSLs and HTSLs) containing the antimicrobial agent ciprofloxacin for temperature-mediated antibiotic release, (2) characterise in vitro ciprofloxacin release and stability and (3) study the efficacy of combining liposomal ciprofloxacin with AMF against Pseudomonas aeruginosa biofilms grown on metal washers. The release of ciprofloxacin from LTSL and HTSL was assessed in physiological buffers. Results demonstrated a lower transition temperature for both LTSL and HTSL formulations when incubated in serum as compared with PBS, with a more pronounced impact on the HTSLs. Upon combining AMF with temperature-sensitive liposomal ciprofloxacin, a 3 log reduction in CFU of Pseudomonas aeruginosa in biofilm was observed. Our initial studies suggest that AMF exposure on metal implants can trigger release of antibiotic from temperature sensitive liposomes for a potent bactericidal effect on biofilm.

Employing high-frequency alternating magnetic fields for the non-invasive treatment of prosthetic joint infections.

Treatment of prosthetic joint infection (PJI) usually requires surgical replacement of the infected joint and weeks of antibiotic therapy, due to the formation of biofilm. We introduce a non-invasive method for thermal destruction of biofilm on metallic implants using high-frequency (>100 kHz) alternating magnetic fields (AMF). In vitro investigations demonstrate a >5-log reduction in bacterial counts after 5 minutes of AMF exposure. Confocal and scanning electron microscopy confirm removal of biofilm matrix components within 1 minute of AMF exposure, and combination studies of antibiotics and AMF demonstrate a 5-log increase in the sensitivity of Pseudomonas aeruginosa to ciprofloxacin. Finite element analysis (FEA) simulations demonstrate that intermittent AMF exposures can achieve uniform surface heating of a prosthetic knee joint. In vivo studies confirm thermal damage is confined to a localized region (<2 mm) around the implant, and safety can be achieved using acoustic monitoring for the presence of surface boiling. These initial studies support the hypothesis that AMF exposures can eradicate biofilm on metal implants, and may enhance the effectiveness of conventional antibiotics.

Radiotherapeutic bandage for the treatment of squamous cell carcinoma of the skin.

INTRODUCTION: Squamous cell carcinoma (SCC) is the second most common form of skin cancer in the United States. The efficacy of a pharmaceutically elegant radiotherapeutic bandage, previously described by us for application against SCC of the skin, was tested for the first time in vivo using a subcutaneous SCC mouse model and a therapeutically relevant radiation dose. METHODS: Female athymic nude mice were injected with human Colo-16 SCC cells subcutaneously and after eight days (average tumor volume: 35±8.6mm(3)) received no treatment, or were exposed to non-radioactive or radioactive (92.5±18.5MBq) bandages for approximately 1h (n=10 per group). After treatment, tumors were measured over fifteen days, tumor volume ratios (TVRs) compared and histopathology performed. RESULTS: Fifteen days after treatment, the TVR of the radioactive bandage treatment group was 3.3±4.5, while TVRs of the non-radioactive bandage treatment and no treatment control groups were 33.2±14.7 and 26.9±12.6, respectively. At the time of necropsy, there was mild focal epidermal hyperplasia surrounding a small area of epidermal ulceration in the radioactive bandage group. No other examined tissue (i.e., muscle, liver, kidney, lung, spleen and heart) showed significant lesions. CONCLUSIONS: Our radiotherapeutic bandage exhibits promising efficacy against SCC of the skin in a mouse model. It can be individually tailored for easy application on tumor lesions of all shapes and sizes, and could complement or possibly replace surgery in the clinic.

Localized delivery of low-density lipoprotein docosahexaenoic acid nanoparticles to the rat brain using focused ultrasound.

Focused ultrasound exposures in the presence of microbubbles can achieve transient, non-invasive, and localized blood-brain barrier (BBB) opening, offering a method for targeted delivery of therapeutic agents into the brain. Low-density lipoprotein (LDL) nanoparticles reconstituted with docosahexaenoic acid (DHA) could have significant therapeutic value in the brain, since DHA is known to be neuroprotective. BBB opening was achieved using pulsed ultrasound exposures in a localized brain region in normal rats, after which LDL nanoparticles containing the fluorescent probe DiR (1,1'-Dioctadecyl-3,3,3',3'-Tetramethylindotricarbocyanine Iodide) or DHA were administered intravenously. Fluorescent imaging of brain tissue from rats administered LDL-DiR demonstrated strong localization of fluorescence signal in the exposed hemisphere. LDL-DHA administration produced 2 × more DHA in the exposed region of the brain, with a corresponding increase in Resolvin D1 levels, indicating DHA was incorporated into cells and metabolized. Histological evaluation did not indicate any evidence of increased tissue damage in exposed brain regions compared to normal brain. This work demonstrates that localized delivery of DHA to the brain is possible using systemically-administered LDL nanoparticles combined with pulsed focused ultrasound exposures in the brain. This technology could be used in regions of acute brain injury or as a means to target infiltrating tumor cells in the brain.

Chemoradiotherapeutic Magnetic Nanoparticles for Targeted Treatment of Nonsmall Cell Lung Cancer.

Lung cancer is the leading cause of cancer-related death in the United States and approximately 85% of all lung cancers are classified as nonsmall cell (NSCLC). We here use an innovative approach that may ultimately allow for the clinician to target tumors and aggressively reduce tumor burden in patients with NSCLC. In this study, a platinum (Pt)-based chemotherapeutic (cisplatin, carboplatin, or oxaliplatin) and holmium-165 (Ho), which can be neutron-activated to produce the holmium-166 radionuclide, have been incorporated together in a garnet magnetic nanoparticle (HoIG-Pt) for selective delivery to tumors using an external magnet. The synthesized magnetic HoIG nanoparticles were characterized using PXRD, TEM, ICP-MS, and neutron-activation. Platinum(II) drugs were incorporated onto HoIG, and these were characterized using FTIR, EDX, ICP-MS, and zeta potential measurements, and in vitro and in vivo studies were performed using a HoIG-platinum system. Results indicate that neutron-activated (166)HoIG-cisplatin is more toxic toward NSCLC A549 cells than is blank (166)HoIG and free cisplatin, and that when an external magnetic field is applied in vivo, higher tumor to liver ratios of Ho are observed than when no magnet is applied, suggesting that magnetic targeting is achieved using this system. Furthermore, an efficacy study demonstrated the inhibition of tumor growth by chemoradiotherapeutic magnetic nanoparticles, compared to no treatment controls.

Nitric oxide- and cisplatin-releasing silica nanoparticles for use against non-small cell lung cancer.

Nitric oxide (NO) and cisplatin releasing wrinkle-structured amine-modified mesoporous silica (AMS) nanoparticles have been developed for the treatment of non-small cell lung cancer (NSCLC). The AMS and NO- and cisplatin-loaded AMS materials were characterized using TEM, BET surface area, FTIR and ICP-MS, and tested in cell culture. The results show that for NSCLC cell lines (i.e., H596 and A549), the toxicity of NO- and cisplatin-loaded silica nanoparticles (NO-Si-DETA-cisplatin-AMS) is significantly higher than that of silica nanoparticles loaded with only cisplatin (Si-DETA-cisplatin-AMS). In contrast, the toxicity of NO-Si-DETA-cisplatin-AMS toward normal lung cell lines is not significantly different from that of Si-DETA-cisplatin-AMS (normal lung fibroblast cells WI-38) or is even lower than that of Si-DETA-cisplatin-AMS (normal lung epithelial cells BEAS-2B). The NO-induced sensitization of tumor cell death demonstrates that NO is a promising enhancer of platinum-based lung cancer therapy.

Radiotherapeutic bandage based on electrospun polyacrylonitrile containing holmium-166 iron garnet nanoparticles for the treatment of skin cancer.

Radiation therapy is used as a primary treatment for inoperable tumors and in patients that cannot or will not undergo surgery. Radioactive holmium-166 ((166)Ho) is a viable candidate for use against skin cancer. Nonradioactive holmium-165 ((165)Ho) iron garnet nanoparticles have been incorporated into a bandage, which, after neutron-activation to (166)Ho, can be applied to a tumor lesion. The (165)Ho iron garnet nanoparticles ((165)HoIG) were synthesized and introduced into polyacrylonitrile (PAN) polymer solutions. The polymer solutions were then electrospun to produce flexible nonwoven bandages, which are stable to neutron-activation. The fiber mats were characterized using scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis and inductively coupled plasma mass spectrometry. The bandages are stable after neutron-activation at a thermal neutron-flux of approximately 3.5 × 10(12) neutrons/cm(2)·s for at least 4 h and 100 °C. Different amounts of radioactivity can be produced by changing the amount of the (165)HoIG nanoparticles inside the bandage and the duration of neutron-activation, which is important for different stages of skin cancer. Furthermore, the radioactive bandage can be easily manipulated to irradiate only the tumor site by cutting the bandage into specific shapes and sizes that cover the tumor prior to neutron-activation. Thus, exposure of healthy cells to high energy ß-particles can be avoided. Moreover, there is no leakage of radioactive material after neutron activation, which is critical for safe handling by healthcare professionals treating skin cancer patients.

Electrospun cellulose acetate-garnet nanocomposite magnetic fibers for bioseparations.

Cellulose acetate fibers with magnetic properties have recently attracted much attention because of their potential novel applications in biomedicine such as for cell and protein separations, magnetic resonance imaging contrast agents, and magnetic filters. In this work, as synthesized yttrium iron garnet and gadolinium substituted yttrium iron garnet nanoparticles have been used to generate magnetic filter paper. Garnet nanoparticles dispersed in cellulose acetate polymer solutions were electrospun as free-standing nonwoven fiber mats as well as on cellulose filter paper substrates resulting in magnetic filter papers. The magnetic fibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and superconducting quantum interference device (SQUID) magnetic property measurements. The resulting magnetic polymer nanocomposites can be easily picked up by an external magnet from a liquid medium. Fluorescein isothiocyanate (FITC) labeled bovine serum albumin (BSA) was separated from solution by using the magnetic filter paper.