Integrated insulin-iron nanoparticles: a multi-modal approach for receptor-specific bioimaging, reactive oxygen species scavenging, and wound healing.

Metallic nanoparticles have emerged as a promising option for various biological applications, owing to their distinct characteristics such as small size, optical properties, and ability to exhibit luminescence. In this study, we have successfully employed a one-pot method to synthesize multifunctional insulin-protected iron [Fe(II)] nanoparticles denoted as [IFe(II)NPs]. The formation of IFe(II)NPs is confirmed by the presence of FTIR bonds at 447.47 and 798.28 cm-1, corresponding to Fe-O and Fe-N bonds, respectively. Detailed analysis of the HR-TEM-EDS-SAED data reveals that the particles are spherical in shape, partially amorphous in nature, and have a diameter of 28.6 ± 5.2 nm. Additionally, Metal Ion Binding (MIB) and Protein Data Bank (PDB) analyses affirm the binding of iron ions to the insulin hexamer. Our findings underscore the potential of IFe(II)NPs as a promising new platform for a variety of biomedical applications due to their high signal-to-noise ratio, and minimal background fluorescence. The particles are highly luminescent, biocompatible, and have a significant quantum yield (0.632). Exemplar applications covered in this paper include insulin receptor recognition and protection against reactive oxygen species (ROS), harmful molecules known to inflict damage on cells and DNA. The IFe(II)NPs effectively mitigate ROS-induced inflammation, which is a hinderance to wound recovery, thereby facilitating enhanced wound recovery.

Zika virus precursor membrane peptides induce immune response in peripheral blood mononuclear cells.

Zika virus is a re-merging flavivirus allied to serious mental health conditions in the fetuses. There is currently no preventives or treatment available for Zika infection. In this work, we have extended the in silico analysis by performing the molecular docking of previous reported three conserved Zika virus precursor membrane (prM) peptides (MP1, MP2 and MP3) with HLA complex (pHLA) and T cell receptors (TCR) and also evaluated the peptide specific immune response in human peripheral blood mononuclear cells (PBMC). Most of the CD8+ and CD4+ T cell peptides-HLA complexes demonstrated good binding energies (ΔG) and HADDOCK scores in molecular docking analysis. Immunogenic response of peptides is measured as human peripheral blood mononuclear cell (PBMC) proliferation and interferon-gamma (IFN-γ) production using a 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and a sandwich enzyme-linked immunosorbent assay (ELISA) respectively on ten different healthy blood samples. Peptide MP3 exhibited significant results in eight (cell proliferation) and seven (IFN-γ secretion) healthy volunteers' blood samples out of ten. Additionally, peptides MP1 and MP2 presented significant cell proliferation and IFN-γ release in six healthy blood samples. Thus, the outcomes from in silico and in vitro studies showed the immunogenic potential of peptides which need to validated in different experimental system before considering as candidate vaccine against Zika virus infection.

Therapeutic potential of lactoferrin-coated iron oxide nanospheres for targeted hyperthermia in gastric cancer.

Lactoferrin (LF) is a non-heme iron-binding glycoprotein involved in the transport of iron in blood plasma. In addition, it has many biological functions, including antibacterial, antiviral, antimicrobial, antiparasitic, and, importantly, antitumor properties. In this study, we have investigated the potential of employing lactoferrin-iron oxide nanoparticles (LF-IONPs) as a treatment modality for gastric cancer. The study confirms the formation of LF-IONPs with a spherical shape and an average size of 5 ± 2 nm, embedded within the protein matrix. FTIR and Raman analysis revealed that the Fe-O bond stabilized the protein particle interactions. Further, we conducted hyperthermia studies to ascertain whether the proposed composite can generate a sufficient rise in temperature at a low frequency. The results confirmed that we can achieve a temperature rise of about 7 °C at 242.4 kHz, which can be further harnessed for gastric cancer treatment. The particles were further tested for their anti-cancer activity on AGS cells, with and without hyperthermia. Results indicate that LF-IONPs (10 µg/ml) significantly enhance cytotoxicity, resulting in the demise of 67.75 ± 5.2% of cells post hyperthermia, while also exhibiting an inhibitory effect on cell migration compared to control cells, with the most inhibition observed after 36 h of treatment. These findings suggest the potential of LF-IONPs in targeted hyperthermia treatment of gastric cancer.

Immunoinformatics-Based Identification of the Conserved Immunogenic Peptides Targeting of Zika Virus Precursor Membrane Protein.

Zika virus infections lead to neurological complications such as congenital Zika syndrome and Guillain-Barré syndrome. Rising Zika infections in newborns and adults have triggered the need for vaccine development. In the current study, the precursor membrane (prM) protein of the Zika virus is explored for its functional importance and design of epitopes enriched conserved peptides with the usage of different immunoinformatics approach. Phylogenetic and mutational analyses inferred that the prM protein is highly conserved. Three conserved peptides containing multiple T and B cell epitopes were designed by employing different epitope prediction algorithms. IEDB population coverage analysis of selected peptides in six different continents has shown the population coverage of 60-99.8% (class I HLA) and 80-100% (class II HLA). Molecular docking of selected peptides/epitopes was carried out with each of class I and II HLA alleles using HADDOCK. A majority of peptide-HLA complex (pHLA) have HADDOCK scores found to be comparable and more than native-HLA complex representing the good binding interaction of peptides to HLA. Molecular dynamics simulation with best docked pHLA complexes revealed that pHLA complexes are stable with RMSD <5.5Å. Current work highlights the importance of prM as a strong antigenic protein and selected peptides have the potential to elicit humoral and cell-mediated immune responses.

Production of a recyclable nanobiocatalyst to synthesize quinazolinone derivatives.

Nanobiocatalysts (NBCs) are an emerging innovation that paves the way toward sustainable and eco-friendly endeavors. In the quest for a robust and reusable nanobiocatalyst, herein, we report a nanobiocatalyst, namely CALB@MrGO, developed via immobilizing Candida antarctica lipase B onto the surface of Fe3O4-decorated reduced graphene oxide (MrGO). Next, the enormous potential of the NBC (CALB@MrGO) was checked by employing it to synthesize clinically important quinazolinone derivatives in good to excellent yield (70-95%) using differently substituted aryl aldehydes with 2-aminobenzamide. Further, the synthetic utility and generality of this protocol was proved by setting up a gram-scale reaction, which afforded the product in 87% yield. The green chemistry metrics calculated for the gram-scale reaction those prove the greenness of this protocol.

Advancement in magnetic hyperthermia-based targeted therapy for cancer treatment.

Magnetic hyperthermia utilizing magnetic nanoparticles (MNPs) and an alternating magnetic field (AMF) represents a promising approach in the field of cancer treatment. Active targeting has emerged as a valuable strategy to enhance the effectiveness and specificity of drug delivery. Active targeting utilizes specific biomarkers that are predominantly found in abundance on cancer cells while being minimally expressed on healthy cells. Current comprehensive review provides an overview of several cancer-specific biomarkers, including human epidermal growth factor, transferrin, folate, luteinizing hormone-releasing hormone, integrin, cluster of differentiation (CD) receptors such as CD90, CD95, CD133, CD20, and CD44 also CXCR4 and vascular endothelial growth factor, these biomarkers bind to ligands present on the surface of MNPs, enabling precise targeting. Additionally, this review touches various combination therapies employed to combat cancer. Magnetic hyperthermia synergistically enhances the efficacy of conventional cancer treatments such as targeted chemotherapy, radiation therapy, gene therapy, and immunotherapy.

Ecotoxicity of as-synthesised copper nanoparticles on soil bacteria.

Release of metallic nanoparticles in soil poses a serious threat to the ecosystem as they can affect the soil properties and impose toxicity on soil microbes that are involved in the biogeochemical cycling. In this work, in vitro ecotoxicity of as-synthesised copper nanoparticles (CuNPs) on Bacillus subtilis (MTCC No. 441) and Pseudomonas fluorescens (MTCC No. 1749), which are commonly present in soil was investigated. Three sets of colloidal CuNPs with identical physical properties were synthesised by chemical reduction method with per batch yield of 0.2, 0.3 and 0.4 gm. Toxicity of CuNPs against these soil bacteria was investigated by MIC (minimum inhibitory concentration), MBC (minimum bactericidal concentration), cytoplasmic leakage and ROS (reactive oxygen species) assay. MIC of CuNPs were in the range of 35-60 µg/ml and 35-55 µg/ml for B. subtilis and P. fluorescens respectively, while their MBC ranged from 40-70 µg/ml and 40-60 µg/ml respectively. MIC and MBC tests reveal that Gram-negative P. fluorescens was more sensitive to CuNPs as compared to Gram positive B. subtilis mainly due to the differences in their cell wall structure and composition. CuNPs with smaller hydrodynamic size (11.34 nm) were highly toxic as revealed by MIC, MBC tests, cytoplasmic leakage and ROS assays, which may be due to the higher active surface area of CuNPs and greater membrane penetration. Leakage of cytoplasmic components and generation of extra-cellular oxidative stress by reactive oxygen species (ROS) causes cell death. The present study realizes in gauging the negative impact of inadvertent release of nanoparticles in the environment, however, in situ experiments to know its overall impact on soil health and soil microflora can help in finding solution to combat ecotoxicity of nanoparticles.

Oxidative Stress Induced Cytotoxicity of Colloidal Copper Nanoparticles on RAW 264.7 Macrophage Cell Line.

Copper is an essential trace mineral that plays an important role in various physiological processes of human body and also possesses excellent antimicrobial properties, however its high dose results in the formation of free-radicals, which can induce cytotoxicity through chromosomal and DNA damage. Therefore, cytotoxicity of colloidal copper nanoparticles (CuNPs) on murine macrophage cell line (RAW 264.7) was studied to understand the correlation between the cytotoxicity and the nanoparticle yield. Three identical sets of CuNPs with similar physical properties having hydrodynamic particle size of 11-14 nm were prepared by chemical reduction method with target yield of 0.2 g, 0.3 g and 0.4 g. CuNPs exhibited dose-dependent (0.001-100 µg/mL) cytotoxicity due to the mitochondrial damage as indicated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assay. Oxidative stress induced by reactive oxygen species (ROS) in RAW 246.7 macrophage cell lines exposed to CuNPs was the primary cause of observed cytotoxicity in all CuNPs test samples. Morphological changes in cells also indicated strong dose-dependent oxidative damage by CuNPs. IC50 (half maximal inhibitory concentration) values of CuNPs were independent of nanoparticle yield. This suggests that per batch variation in CuNPs yield from 0.2 g to 0.4 g had no negative correlation with their toxicity that makes CuNPs a potential candidate for further development of nanotherapeutics and anticancer drugs.

Nanoantibiotics: strategic assets in the fight against drug-resistant superbugs.

Antimicrobial characteristics of metals reveal that Ag despite its economic constraints remains the most popular antibiotic agent. Antimicrobial characteristics of copper nanoparticles (CNPs) are not well understood. To our knowledge, no systematic comparative study on microbial properties of silver nanoparticles (SNPs) and CNPs exists. In this article, a comparative study on microbial properties of engineered metal nanoantibiotics against clinically important strains has been attempted. Our results indicate that biocidal activities of CNPs are better than SNPs. Minimum inhibitory concentration (MIC) values of CNPs are 10 times lower than the corresponding MICs of SNPs. These improved biocidal activities of CNPs would make it affordable and potent nontraditional antibiotics against which microbes are least susceptible to develop any drug resistance.

Effect of Colloidal Medium on the Shelf-Life and Stability of Gold Nanorods Prepared by Seed-Mediated Synthesis.

Gold nanorods (GNRs) owing to their tunable longitudinal surface plasmon resonance in tissue transparent near infrared region have potential applications (like cancer imaging, surface enhanced Raman spectroscopy, cancer targeting, drug delivery and optical hyperthermia) in nanomedicine. Success of these diagnosis/therapy options depends on the plasmonic properties of gold nanorods, which are influenced by the interaction of GNRs with the colloidal medium. In this article, a systematic study is performed to evaluate the effect of colloidal medium on shelf life and stability of gold GNRs. As-synthesized GNRs are preserved in four aqueous media (deionized water, pluronic F-127, CTAB solution and growth solution) and their stability is investigated by closely monitoring the changes in the plasmonic signatures by UV-Visible spectroscopy and variation in hydrodynamic size by photon correlation spectroscopy for 30 days. As-synthesized GNRs are most stable in deionized water followed by pluronic F-127, CTAB and growth solution. The vast difference in the colloidal stability of GNRs in different media is due to the differences in surface driven unzipping of gold in these aqueous media.

Influence of antibiotic adsorption on biocidal activities of silver nanoparticles.

Excessive use of antibiotics has posed two major challenges in public healthcare. One of them is associated with the development of multi-drug resistance while the other one is linked to side effects. In the present investigation, the authors report an innovative approach to tackle the challenges of multi-drug resistance and acute toxicity of antibiotics by using antibiotics adsorbed metal nanoparticles. Monodisperse silver nanoparticles (SNPs) have been synthesised by two-step process. In the first step, SNPs were prepared by chemical reduction of AgNO3 with oleylamine and in the second step, oleylamine capped SNPs were phase-transferred into an aqueous medium by ligand exchange. Antibiotics - tetracycline and kanamycin were further adsorbed on the surface of SNPs. Antibacterial activities of SNPs and antibiotic adsorbed SNPs have been investigated on gram-positive (Staphylococcus aureus, Bacillus megaterium, Bacillus subtilis), and gram-negative (Proteus vulgaris, Shigella sonnei, Pseudomonas fluorescens) bacterial strains. Synergistic effect of SNPs on antibacterial activities of tetracycline and kanamycin has been observed. Biocidal activity of tetracycline is improved by 0-346% when adsorbed on SNPs; while for kanamycin, the improvement is 110-289%. This synergistic effect of SNPs on biocidal activities of antibiotics may be helpful in reducing their effective dosages.

Antibacterial activities of silver nanoparticles and antibiotic-adsorbed silver nanoparticles against biorecycling microbes.

Silver nanoparticles have a huge share in nanotechnology based products used in clinical and hygiene products. Silver nanoparticles leaching from these medical and domestic products will eventually enter terrestrial ecosystems and will interact with the microbes present in the land and water. These interactions could be a threat to biorecycling microbes present in the Earth's crust. The antimicrobial action towards biorecycling microbes by leached silver nanoparticles from medical waste could be many times greater compared to that of silver nanoparticles leached from other domestic products, since medical products may contain traditional antibiotics along with silver nanoparticles. In the present article, we have evaluated the antimicrobial activities of as-synthesized silver nanoparticles, antibiotics - tetracycline and kanamycin, and antibiotic-adsorbed silver nanoparticles. The antimicrobial action of silver nanoparticles with adsorbed antibiotics is 33-100% more profound against the biorecycling microbes B. subtilis and Pseudomonas compared to the antibacterial action of silver nanoparticles of the same concentration. This study indicates that there is an immediate and urgent need for well-defined protocols for environmental exposure to silver nanoparticles, as the use of silver nanoparticles in nanotechnology based products is poorly restricted.

Antibacterial activity of silver: the role of hydrodynamic particle size at nanoscale.

Silver shows the highest antimicrobial activities amongst all metals. It is better than many first line antibiotics. The antimicrobial properties of silver can be tuned by altering its physical and surface properties. Researchers have demonstrated enhancement in the antibacterial properties of silver with decreasing particle size from bulk to nano. In the present article, we study the effect of particle size of silver at nanoscale on their antimicrobial properties. Two samples of silver nanoparticles (SNPs) of same physical size (≈8 nm) but different hydrodynamic size (59 and 83 nm) are prepared by chemical reduction of AgNO3 with oleylamine followed by phase transfer with triblock copolymer Pluronic F-127. Their antimicrobial properties are investigated by microdilution method against clinically important strains of gram positive (S. aureus and B. megaterium) and gram negative (P. vulgaris and S. sonnei) bacteria. Nearly 38-50% enhancement in the antibacterial action of SNPs was observed when their hydrodynamic size was reduced to 59 nm from 83 nm. It has been observed that the antibacterial action of SNPs was governed by their hydrodynamic size and not by their crystallite and physical size. The phenomenological model was also proposed which makes an attempt to explain the microscopic mechanism responsible for the size dependent antibacterial activities of silver.

Hydrodynamics of chains in ferrofluid-based magnetorheological fluids under rotating magnetic field.

Ferrofluid-based magnetorheological (MR) fluid is prepared by dispersing micron-size magnetic spheres in a ferrofluid. We report here the mechanism of chain formation in ferrofluid based MR fluid, which is quite different from conventional MR fluid. Some of the nanomagnetic particles of ferrofluid filled inside the microcavities are formed due to association of large particles, and some of them are attached at the end of large particles. Under rotating magnetic field, fragmentation of a single chain into three parts is observed. Two of them are chains of micron-size magnetic particles which are suspended in a ferrofluid, and the third one is the chain of nanomagnetic particles of ferrofluid, which may be the connecting bridge between the two chains of larger magnetic particles. The rupture of a single chain provides evidence for the presence of nanomagnetic particles within the magnetic field-induced chainlike structure in this bidispersed MR fluid.

Experimental investigation of magnetically induced unusual emission of light from a ferrodispersion.

An unusual emission of light is observed when a coherent light beam is passed through a mixture of a magnetorheological suspension and a ferrofluid that is subjected to a critical magnetic field. When first the incident light is removed and then the field is switched off, a flash of light is observed. In this Letter certain characteristics of this unusual emission are reported. Our findings suggest that a part of the incident light energy is magnetically trapped within the medium. Upon removal of the field, the same is released. Several physical phenomena that may give rise to such emission are discussed. The magnetically tunable emission will be useful to develop photonic devices.

Field induced rotational viscosity of ferrofluid: effect of capillary size and magnetic field direction.

In the present investigation we report the effect of capillary diameter and the direction of applied magnetic field on the rotational viscosity of water and kerosene based ferrofluids. We found that changes in the field induced rotational viscosity are larger in the case of water based magnetic fluid than that of kerosene based fluid. The field induced rotational viscosity is found to be inversely proportional to the capillary diameter and it falls exponentially as a function of the angle between the direction of field and vorticity of flow. Magnetophoretic mobility and hydrodynamic volume fraction of nanomagnetic particles are determined for above cases.