Synthetically Tunable Suprahybrid Nanoparticle Platform for the Efficacious Delivery of Therapeutics.

The discovery of lipid-hybrid nanosystems has offered potential solutions to various drug delivery and theranostic challenges. However, in many instances, the commonly used lipids and other components in these systems often pose challenges related to their solubility, physicochemical properties, immune compatibility, and limited synthetic tunability. In this work, we introduce a synthetically tunable supramolecular scaffold with amphiphilic characteristics based on the calix[4]arene macrocyclic system. We designed and synthesized two novel calix[4]arene-polyethylene glycol (PEG) conjugates, termed Cal-P1 and Cal-P2, and these were characterized utilizing a wide range of spectroscopic and analytical methods. The rational design of Cal-P1 and Cal-P2 demonstrates their utility in forming stable blended nanospheres with sustained drug release characteristics. The synergistic blending of PLGA and the calixarene scaffold (Cal-P1 and Cal-P2) in constructing long-lasting and controlled-release nanoparticles (NPs), which are optimized for encapsulating Nile Red dye, and their successful internalization and retention in HeLa cancer cells are demonstrated through in vitro assays. The potential of these NPs as sustained therapeutic carriers is investigated in vivo, showing improved retention compared to free dye with negligible toxicity. The successful design and construction of Cal-P1 and Cal-P2 nanosystems represent a new paradigm for addressing drug loading challenges, opening up opportunities for the development of highly efficient, synthetically tunable alternative adjuvants for drug encapsulation and delivery.

Trace elements dyshomeostasis in liver and brain of weanling mice under altered dietary selenium conditions.

BACKGROUND: A balanced diet containing selenium (Se) and other trace elements is essential for normal development and growth. Se has been recognized as an essential trace element; however, its interaction with other elements has not been fully investigated. In the present study, sodium (Na), magnesium (Mg), potassium (K), calcium (Ca), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), Se and rubidium (Rb), were analysed in liver and brain regions under altered dietary Se intake in weanling mice to identify major discriminatory elements. METHODS: The study investigated the effects of different levels of Se intake on the elemental composition in liver and brain tissues of weaned mice. After 24 weeks of feeding with Se adequate, deficient, and excess diets, elemental analysis was performed on the harvested tissues using Inductively coupled plasma mass spectrometry (ICP-MS). Statistical analysis that included analysis of covariance (ANCOVA), correlation coefficient analysis, principal component analysis, and partial least squares discriminant analysis were performed. RESULTS: The ANCOVA showed statistically significant changes and correlations among the analysed elements under altered dietary Se status. The multivariate analysis showed differential changes in elements in liver and brain regions. The results suggest that long-term dietary Se alternations lead to dyshomeostasis in trace elements that are required in higher concentrations compared to Se. It was observed that changes in the Fe, Co, and Rb levels were similar in all the tissues studied, whereas the changes in Mg, Cr, and Mn levels were different among the tissues under altered dietary Se status. Additionally, the changes in Rb levels correlated with the dietary Se intake but had no relation with the tissue Se levels. CONCLUSIONS: The findings suggest interactions between Mg, Cr, Mn, Fe, Co, and Se under altered Se status may impact cellular functions during postnatal development. However, the possible biological significance of alterations in Rb levels under different dietary Se paradigms needs to be further explored.

Nano-Biotechnology for Bacteria Identification and Potent Anti-bacterial Properties: A Review of Current State of the Art.

Sepsis is a critical disease caused by the abrupt increase of bacteria in human blood, which subsequently causes a cytokine storm. Early identification of bacteria is critical to treating a patient with proper antibiotics to avoid sepsis. However, conventional culture-based identification takes a long time. Polymerase chain reaction (PCR) is not so successful because of the complexity and similarity in the genome sequence of some bacterial species, making it difficult to design primers and thus less suitable for rapid bacterial identification. To address these issues, several new technologies have been developed. Recent advances in nanotechnology have shown great potential for fast and accurate bacterial identification. The most promising strategy in nanotechnology involves the use of nanoparticles, which has led to the advancement of highly specific and sensitive biosensors capable of detecting and identifying bacteria even at low concentrations in very little time. The primary drawback of conventional antibiotics is the potential for antimicrobial resistance, which can lead to the development of superbacteria, making them difficult to treat. The incorporation of diverse nanomaterials and designs of nanomaterials has been utilized to kill bacteria efficiently. Nanomaterials with distinct physicochemical properties, such as optical and magnetic properties, including plasmonic and magnetic nanoparticles, have been extensively studied for their potential to efficiently kill bacteria. In this review, we are emphasizing the recent advances in nano-biotechnologies for bacterial identification and anti-bacterial properties. The basic principles of new technologies, as well as their future challenges, have been discussed.

Multiepitope glycan based laser assisted fluorescent nanocomposite with dual functionality for sensing and ablation of Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) infection is becoming a severe health hazard and needs early diagnosis with high specificity. However, the non-specific binding of a biosensor is a challenge to the current bacterial detection system. For the first time, we chemically synthesized a galactose tripod (GT) as a P. aeruginosa-specific ligand. We conjugated GT to a photothermally active fluorescent nanocomposite (Au@SiO2-TCPP). P. aeruginosa can be detected using Au@SiO2-TCPP-GT, and additionally ablated as well using synergistic photothermal and photodynamic therapy. Molecular dynamics and simulation studies suggested better binding of GT (binding energy = -6.6 kcal mol-1) with P. aeruginosa lectin than that of galactose monopod (GM) (binding energy = -5.9 kcal mol-1). Furthermore, a binding study was extended to target P. aeruginosa, which has a galactose-binding carbohydrate recognition domain receptor. The colorimetric assay confirmed a limit of detection (LOD) of 104 CFU mL-1. We also looked into the photosensitizing property of Au@SiO2-TCPP-GT, which is stimulated by laser light (630 nm) and causes photoablation of bacteria by the formation of singlet oxygen in the surrounding media. The cytocompatibility of Au@SiO2-TCPP-GT was confirmed using cytotoxicity assays on mammalian cell lines. Moreover, Au@SiO2-TCPP-GT also showed non-hemolytic activity. Considering the toxicity analysis and efficacy of the synthesized glycan nanocomposites, these can be utilized for the treatment of P. aeruginosa-infected wounds. Furthermore, the current glycan nanocomposites can be used for bacterial detection and ablation of P. aeruginosa in contaminated food and water samples as well.

Triazole-Peptide Conjugate as a Modulator of Aß-Aggregation, Metal-Mediated Aß-Aggregation, and Cytotoxicity.

Amyloid-ß (Aß) aggregation plays a key role in the pathogenesis of Alzheimer's disease (AD). Along with this, the presence of redox-active metals like Cu2+ further enhances Aß aggregation, oxidative stress, and cellular toxicity. In this study, we have rationally designed, synthesized, and evaluated a series of triazole-peptide conjugates as potential promiscuous ligands capable of targeting different pathological factors of AD. In particular, peptidomimetic DS2 showed the best inhibitory activity against Aß aggregation with an IC50 value of 2.43 ± 0.05 µM. In addition, DS2 disaggregates preformed Aß42 fibrils, chelates metal ions, inhibits metal-mediated Aß aggregation, significantly controls reactive oxygen species production, and reduces oxidative stress. DS2 exhibited very low cytotoxicity and significantly ameliorated the Aß-induced toxicity in differentiated neuroblastoma cells, SH-SY5Y. In addition, alteration in the fibrillary architecture of Aß42 in the absence and presence of DS2 was validated by transmission electron microscopy (TEM) images. To shed light on the inhibitory mechanism of DS2 against Aß aggregation and disassembly of the protofibril structure, molecular dynamics (MD) simulations have been performed. DS2 binds preferentially with the central hydrophobic core (CHC) residues of Aß42 monomer and chains D-E of Aß42 protofibril. The dictionary of secondary structure of proteins analysis indicated a noteworthy increase in the helix content from 38.5 to 61% and, notably, a complete loss of ß-sheet content of Aß42 monomer when DS2 is added to it. DS2 suppressed Aß42 monomer aggregation by preserving helical conformations and was able to reduce the production of aggregation-prone ß-sheet structures, which are consistent with ThT, circular dichroism, and TEM assay that indicate a reduction in the formation of toxic Aß42 aggregated species on the addition of DS2. Moreover, DS2 destabilized the Aß42 protofibril structure by significantly reducing the binding affinity between chains D-E of protofibril, which highlighted the disruption of interchain interactions and subsequent deformation of the protofibril structure. The results of the present study demonstrate that triazole-peptide conjugates may be valuable chemotypes for the development of promising multifunctional AD therapeutic candidates.

Mechanobactericidal, Gold Nanostar Hydrogel-Based Bandage for Bacteria-Infected Skin Wound Healing.

The emergence of multidrug resistant (MDR) microorganisms has led to the development of alternative approaches for providing relief from microbial attacks. The mechano-bactericidal action as a substitute for antimicrobials has become the focus of intensive research. In this work, nanostructure-conjugated hydrogel are explored as a flexible dressing against Staphylococcus aureus (S. aureus)-infected skin wounds. Herein gold nanostars (AuNst) with spike lengths reaching 120 nm are probed for antibacterial action. The bacterial killing of >95% is observed for Pseudomonas aeruginosa (P. aeruginosa) and Escherichia coli (E. coli), while up to 60% for Gram-positive S. aureus. AuNst conjugated hydrogel (AuNst120@H) reduced >80% colonies of P. aeruginosa and E. coli. In comparison, around 35.4% reduction of colonies are obtained for S. aureus. The viability assay confirmed the presence of about 85% of living NIH-3T3 cells when grown with hydrogels. An animal wound model is also developed to assess the efficiency of AuNst120@H. A significant reduction in wound size is observed on the 10th day in AuNst120@H treated animals with fully formed epidermal layers, hair follicles, new blood vessels, and arrector muscles. These findings suggest that novel dressing materials can be developed with antimicrobial nanotextured surfaces.

Insight into the antifungal effect of chitosan-conjugated metal oxide nanoparticles decorated on cellulosic foam filter for water filtration.

Worldwide, fungal contamination of water resources has become a major threat to both human health and the environment. The adaptation of nanotechnology in conventional water processes is significant to offer new breakthroughs in water treatment, especially fungal contaminants. Chitosan conjugated metal oxide nanoparticles can affect the antimicrobial properties of cellulosic foam. In the present study, three different types of biocompatible nanoconjugates (i.e., ZnO/chitosan, CuO/chitosan, and Ag2O/chitosan) were synthesized for functionalization of five differently processed cellulose foam filters for resisting fungal spores during water treatment. To evaluate the antifungal effect of these nanoconjugates against prevalent strains of Aspergillus niger (A. niger), Aspergillus flavus (A. flavus), and Rhizopus oryzae (R. oryzae), the stable coating was introduced on different cellulose filter papers through impregnation. The statistical analysis of antifungal experiment was carried out by two-way factorial ANOVA test. Cellulose filter containing ZnO/chitosan displayed a stronger antifungal behavior in disc diffusion method than those impregnated with CuO/chitosan, and Ag2O/chitosan nanoconjugates. Besides the choice of nanoconjugates, the variation in cellulose foam filters (in terms of concentration of their raw materials and/or processing methodology) can also affect their antifungal performance. Further, the assessment of cytotoxic nature of such nanocomposites-modified cellulose foam filters is a fundamental step towards their real field applications.

Nanoglycocluster based diagnostic platform for colorimetric detection of bacteria; A comparative study analysing the effect of AuNPs size, linker length, and glycan diversity.

Nanoglycoclusters, an upcoming class of functional nanomaterial are known to drive various processes like detection, imaging, targeting proteins, cells, and bacteria. Nanoglycoclusters are a type of nanomaterial functionalized with various glycans. The array of glycan in multiple copies enhances binding affinity with proteins. Selective and sensitive bacteria/lectin interactions using nanomaterials are an emerging area of research. The measurement of different ligand receptor interactions require sophisticated analytical tools that limit the application in biosensor domain. Recently, colorimetric biosensors gained importance in the field of the biosensor for the detection of bacteria/lectins. Herein we have demonstrated that different size of gold nanoparticles (AuNPs) along with various polyethylene glycol (PEG) linkers, functionalized with synthesized monopod and tripod of mannose and galactose that have different bacteria/lectins specificity. The newly synthesized nanoglycoclusters were able to discriminate between different lectins and bacteria. The aggregation of specific nanoglycocluster upon interaction with specific bacteria/lectins revealed that mannose monopod (MM) and mannose tripod (MT) are specific to Escherichia coli and concanavalin A (ConA) lectin, while galactose monopod (GM) and galactose tripod (GT) are specific to Pseudomonas aeruginosa and Peanut agglutinin (PNA) lectin. Further, the binding events depict the affinity of tripod glycans is more with respect to its corresponding monopod glycans. Our findings explored the potential of colorimetric sensing depending upon the size of AuNPs, linker length, specificity, along with glycans density to develop user friendly diagnostic system for the detection of bacteria.

Graphene oxide and fluorescent aptamer based novel biosensor for detection of 25-hydroxyvitamin D3.

For maintaining the healthy metabolic status, vitamin D is a beneficial metabolite stored majorly in its pre-activated form, 25-hydroxyvitamin D3 (25(OH)D3). Due to its important role in bone strengthening, the study was planned to quantify 25(OH)D3 levels in our blood. Quantification techniques for 25(OH)D3 are costly thus requiring a need for a low cost, and sensitive detection methods. In this work, an economic, and sensitive sensor for the detection of 25(OH)D3 was developed using aptamer and graphene oxide (GO). Aptamer is an oligonucleotide, sensitive towards its target, whereas, GO with 2D nanosheets provides excellent quenching surface. Aptamer labeled with fluorescein (5', 6-FAM) is adsorbed by π-π interaction on the GO sheets leading to quenching of the fluorescence due to Förster resonance energy transfer (FRET). However, in the presence of 25(OH)D3, a major portion of aptamer fluorescence remains unaltered, due to its association with 25(OH)D3. However, in the absence, aptamer fluorescence gets fully quenched. Fluorescence intensity quenching was monitored using fluorescence spectrophotometer and agarose gel based system. The limit of detection of 25(OH)D3 by this method was found to be 0.15 µg/mL whereas when GO-COOH was used, limit of detection was improved to 0.075 µg/mL. Therefore, this method could come up as a new sensing method in the field of vitamin D detection.

Nanomaze Lure: Pheromone Sandwich in Graphene Oxide Interlayers for Sustainable Targeted Pest Control.

The indiscriminate use of pesticides leads to irreparable damage to the ecosystem, which motivates for sustainable alternatives like pheromone-assisted pest management. The tomato pinworm Tuta absoluta is a major threat to tomato cultivation. Moreover, its green management technology uses a pheromone trap that has a short field life. To overcome this problem, a pheromone composite with graphene oxide (GO) and amine-modified graphene oxide (AGO) that can extend the diffusion path has been developed. The composite stimulates an effective electrophysiological response in the antenna, which results in trapping of a significantly higher number of insects as compared to the commercial septa, thus qualifying it for field evaluation. Compared to AGO, the GO composite has pheromones assembled into a multilayer, which increases the pheromone diffusion path. This in turn resulted in the extension of the pheromone life that proportionally increased the pest trapped. This technique will be beneficial to farmers as they have longer field efficacy to keep the pest damage low in an environmentally friendly manner.

Effect of hepcidin antagonists on anemia during inflammatory disorders.

Iron is an essential element for the mammalian body however, its homeostasis must be regulated accurately for appropriate physiological functioning. Alterations in physiological iron levels can lead to moderate to severe iron disorders like chronic and acute iron deficiency (anemia) or iron overload. Hepcidin plays an important role in regulating homeostasis between circulating iron and stored iron in the cells as well as the absorption of dietary iron in the intestine. Inflammatory disorders restrict iron absorption from food due to increased circulating levels of hepcidin. Increased production of hepcidin causes ubiquitination of ferroportin (FPN) leading to its degradation, thereby retaining iron in the spleen, duodenal enterocytes, macrophages, and hepatocytes. Hepcidin inhibitors and antagonists play a consequential role to ameliorate inflammation-associated anemia. Many natural and synthesized compounds, able to reduce hepcidin expression during inflammation have been identified in recent years. Few of which are currently at various phases of clinical trial. This article comprises a comprehensive review of therapeutic approaches for the efficient treatment of anemia associated with inflammation. Many strategies have been developed targeting the hepcidin-FPN axis to rectify iron disorders. Hepcidin modulation with siRNAs, antibodies, chemical compounds, and plant extracts provides new insights for developing advanced therapeutics for iron-related disorders. Hepcidin antagonist's treatment has a high potential to improve iron status in patients with iron disorders, but their clinical success needs further recognition along with the identification and application of new therapeutic approaches.

Potential benefits of phytochemicals from Azadirachta indica against neurological disorders.

Azadirachta indica or Neem has been extensively used in the Indian traditional medical system because of its broad range of medicinal properties. Neem contains many chemically diverse and structurally complex phytochemicals such as limonoids, flavonoids, phenols, catechins, gallic acid, polyphenols, nimbins. These phytochemicals possess vast array of therapeutic activities that include anti-feedant, anti-viral, anti-malarial, anti-bacterial, anti-cancer properties. In recent years, many phytochemicals from Neem have been shown to be beneficial against various neurological disorders like Alzheimer's and Parkinson's disease, mood disorders, ischemic-reperfusion injury. The neuroprotective effects of the phytochemicals from Neem are primarily mediated by their anti-oxidant, anti-inflammatory and anti-apoptotic activities along with their ability to modulate signaling pathways. However, extensive studies are still required to fully understand the molecular mechanisms involved in neuropotective effects of phytochemicals from Neem. This review is an attempt to cover the neuroprotective properties of various phytochemicals from Neem along with their mechanism of action so that the potential of the compounds could be realized to reduce the burden of neurodegenerative diseases.

pH-Triggered, Synbiotic Hydrogel Beads for In Vivo Therapy of Iron Deficiency Anemia and Reduced Inflammatory Response.

Iron deficiency anemia (IDA) is the most common nutritional disorder worldwide nearly affecting two billion people. The efficacies of conventional oral iron supplements are mixed, intravenous iron administration acquaintances with finite but crucial risks. Usually, only 5-20% iron is absorbed in the duodenum while the remaining fraction reaches the colon, affecting the gut microbes and can significantly impact intestinal inflammatory responses. Therefore, administration of gut bacterial modulators such as probiotics, prebiotics, and any other dietary molecules that can stimulate healthy gut bacteria can enhance iron absorption without any adverse side effects. In this study, we have prepared an iron supplement to avoid the side effects of conventional oral iron supplements. The formulation includes co-encapsulation of iron with anti-inflammatory probiotic bacteria within alginate/starch hydrogels (B + I-Dex (H)), which has been demonstrated to be efficient in mitigating IDA in vivo. As intestinal pH increases, the pore size of hydrogel increases due to ionic interactions and thus releases the encapsulated bacteria and iron. The field emission scanning electron microscopy (FESEM) analysis confirmed the porous structure of hydrogel beads, and in vitro release studies showed a sustained release of iron and bacteria at intestinal pH. The hydrogel was found to be nontoxic and biocompatible in Caco2 cell lines. The formulation showed efficient in vitro and in vivo iron bioavailability in Fe depletion-repletion studies. B + I-Dex (H) was observed to generate less inflammatory response than FeSO4 or nonencapsulated iron dextran (I-Dex) in vivo. We entrust that this duly functional hydrogel formulation could be further utilized or modified for the development of oral therapeutics for IDA.

Liver Phosphoenolpyruvate Carboxykinase-1 Downregulation via siRNA-Functionalized Graphene Oxide Nanosheets Restores Glucose Homeostasis in a Type 2 Diabetes Mellitus In Vivo Model.

Metabolic disorders have been increasing at an alarming rate, and one such example of metabolic disorder is type 2 diabetes mellitus (T2DM). Unregulated gluconeogenesis in T2DM results in increased hepatic glucose output that causes fasting and postprandial hyperglycaemia. Extensive proofs have shown that the downregulation of the key rate-limiting enzyme phosphoenolpyruvate carboxykinase-1 (PCK-1) of gluconeogenesis improved glucose homeostasis in vivo. In the present study, we have synthesized and characterized liver-specific stearic acid conjugated octaarginine (StA-R8) functionalized 4arm-2K-PEGamineylated graphene oxide nanosheets (GPR8) for the delivery of siRNA against PCK-1 in T2DM C57BL/6 mice. We found that a single intravenous administration of siRNA (3 mg/kg BW) conjugated to GPR8 (GPR8:PCK-1siRNA(3 mg/kg BW) conjugate) in an optimized N/P ratio exploited as a therapeutic nanoformulation maintained glucose homeostasis for nearly 4 weeks in the T2DM mice. Efficient silencing of PCK-1 in T2DM liver tissue increased the phosphorylation of serine-256 of FOXO-1, thus showing a marked decrease in hepatic gluconeogenesis. Gluconeogenesis control and consequently glucose output from the liver furthermore partially enhanced liver and muscle insulin sensitivity results in the stimulation of the insulin/AKT-2 signaling pathway which indirectly restored glucose homeostasis in the treated T2DM group. Our therapeutic nanoformulation also improved glycogen storage in the liver and membrane translocation of GLUT4 in the muscle of the treated T2DM group. In conclusion, GPR8:PCK-1siRNA (3 mg/Kg BW) restored glucose homeostasis by controlling the hepatic glucose production and improved peripheral insulin sensitivity as a consequence of reduced hyperglycemia. Thus, the current approach offered an alternative strategy for the therapeutics for T2DM.

1,2,3-Triazole ß-lactam conjugates as antimicrobial agents.

A convenient and efficient synthesis of new triazole ß-lactam conjugates using click chemistry is described. ß-lactam 15 and 16 were prepared using cycloaddition strategy and propargylated at N-1 to afford compounds 17 and 18. Cu-catalyzed click reaction of these ß-lactams 17 and 18 with different aryl azides provided 1,2,3-triazole conjugates 6 and 7, respectively. The products were fully characterized spectroscopically and tested against Gram-(+) and Gram-(-) bacteria. Compound 7a and 7c were found to be most active.

Physicochemical, in-vitro therapeutic activity and biomolecular interaction studies of Mn(II), Ni(II) and Cu(II) complexes tethered with O2N2 ligand backbone.

Two major health crisis of today's world are antimicrobial drug resistance and type II diabetes. To tackle them, there is an immediate requirement for the development of new and safer drugs and the present work is one such quest for novel and efficient drug candidates. We have developed three trace metal coordination compounds tethered with a reduced salen ligand {H2(hpdbal)2-an} (L), namely, a manganese-salan complex, [MnII(H2O)2{(hpdbal)2-an}] (1), a nickel-salan complex, [NiII{(hpdbal)2-an}] (2) and a copper-salan complex, [CuII{(hpdbal)2-an}] (3). The compounds were characterized by elemental analysis, vibrational spectroscopy, electronic spectroscopy, thermogravimetric analysis, nuclear magnetic resonance and electron-paramagnetic resonance techniques. The compounds were evaluated for antimicrobial activity against seven pathogens (Escherichia coli, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans and Cryptococcus neoformans) and antidiabetic activity by mimicking diabetic environment on the immortal human liver cancer cells, HepG2. Complexes 1 and 2 were additionally tested for their reactivity and stability in biological media mimic conditions. The nickel(II) salan complex (2) exhibited noteworthy antifungal activity against Candida albicans and the manganese(II) salan complex (1) induced increased glucose uptake by the insulin resistant cells. Both compounds were found to be stable when solution pH conditions were varied from 3 to 9. They exhibited strong affinity of binding towards a carrier protein, bovine serum albumin which was evaluated with the aid of multi-spectroscopic techniques.

A manganese (II) complex tethered with S-benzyldithiocarbazate Schiff base: Synthesis, characterization, in-vitro therapeutic activity and protein interaction studies.

There is an urgent need to eliminate the era of superbugs through design and development of novel and sustainable drugs. Transition metal complexes can be one of the hopes for tackling drug resistant pathogens. In this view, we have developed a manganese complex appended with an ON donor ligand which has shown excellent activity against one of the prominent fungal species. The Mn (II) complex, [MnII(OH2)2(Hhpdbal-sbdt)2] (1) was synthesized using a Schiff base ligand derived from an azo aldehyde and S-benzyldithiocarbazate. The complex was characterized with the help of analytical techniques such as elemental analysis, FT-IR, EDAX, EPR and TGA. The solution behavior in physiological conditions and in biological media was preliminarily evaluated by studying the behavior of complex in varied pH conditions and in the presence of protein, BSA. The effect of the compound on few drug resistant pathogenic species of bacteria and fungi and on the uptake of glucose by insulin resistant cells was evaluated using whole cell inhibition assay and NBDG assay respectively. The study gave a noteworthy result with respect to the manganese compound's biological activity, with an inhibitory activity of 93% towards a fungi species, Cryptococcus neoformans and with a relatively good glucose uptake inducing capacity. The manganese complex, which maintains its stability over a wide range of pH conditions and interacts with serum protein, BSA in a facile manner can be an excellent drug candidate and eventually be added to the library of compounds being screened for in vivo activity studies.

Organophosphonate functionalized Au/Si@Fe3O4: Versatile carrier for enzyme immobilization.

Magnetic nanoparticles with silica/gold (Au) shell were synthesized to be used as substrates for enzyme immobilization. Successful functionalization was followed by addition of phosphate linkers containing carboxyl end as free end for linking with enzyme. Effect of varied phospho-carboxyl chain lengths based linkers, 3-phosphonopropionic acid (3-PPA) and 16-phosphonopropionic acid (16-PHDA) on kinetic parameters of enzyme were studied. Immobilization of upto 670µg/mg of nanoparticles were observed. Enzyme bound with longer chain linker were observed to have Km (11.8mg/mL) and Vmax (1.59µmol/min/mg) which was found to be lower than 3-PPA. Reusability assay gave a minimum of 70% activity at 10th time of usage. Thus, an efficient, robust, cost effective and easily separable substrate for restraining the enzyme was prepared.

Sensible graphene oxide differentiates macrophages and Leishmania: a bio-nano interplay in attenuating intracellular parasite.

Leishmania is an obligate intracellular protozoan parasite, which resides in human macrophage vacuoles that are referred to as parasitophorus vacuoles. Amphotericin B (AmB) is the first-line drug with 99% cure rates; however, overdose-induced toxic side effects are a major limitation. To improve the efficacy at lower dose and subsequently to avoid toxicity and to further investigate the role of charge dynamics on the efficacy, a graphene oxide (GO)-based composite of AmB was developed with native negatively charged GO and amine-conjugated positively charged AGO. The AGO composite resulted in enhanced uptake as confirmed by confocal and FACS analysis. Thus, AGO caused a strong inhibition of amastigotes, with IC50 values 5-fold lower than free AmB. The parasitophorus vacuoles harbour a hydrolytic and acidic environment, which is favourable for the parasites, as they don't attenuate this condition. AGO-AmB was able to modify the intracellular pH of the Leishmania donovani-infected macrophages, generating unfavourable conditions for the amastigote, and thus improving its efficacy.