Evaluation of liver specific ionizable lipid nanocarrier in the delivery of siRNA.

Hepcidin, a key regulator of iron homeostasis, has been implicated in the pathogenesis of various iron-related diseases. Although small interfering RNA (siRNA) are potent to modulate the expression of hepcidin, their bioavailability remains a major issue. The ß-galactopyranoside-conjugated liposomes (GAL-liposome) targeting liver synthesized hepcidin were prepared by thin lipid film hydration method to encapsulate siRNA and the conjugation of ß-galactopyranoside to the lipid nanocarrier was achieved by covalent chemistry. The prepared siRNA loaded GAL-lip were spherical with around 50 nm radius in size as observed by HR-TEM. The zeta potential and polydispersity index of the prepared liposomes were - 19.9 ± 0.96 mV and 0.44 ± 0.05, respectively. The encapsulation efficiency as determined by dialysis bag method was around 91.76 ± 1.74%. The cell viability and cellular uptake analysis was examined in HepG2 cells by MTT assay and flow cytometry, respectively. The stability and cumulative release of siRNA was also assessed. The hepcidin mRNA expression on administration of siRNA loaded GAL-lip was determined in HepG2 cells and in lipopolysaccharide-induced mice model followed by examining itsin vivo biodistribution by fluorescence microscopy. The results suggested thatsiRNA loaded GAL-lip reduced the hepcidin levels, thus, highlighting a novel ligand conjugated ionizable lipid-based nanocarrier for inducing RNA interference.

Recent trends in 2D materials and their polymer composites for effectively harnessing mechanical energy.

Self-powered wearable devices, with the energy harvester as a source of energy that can scavenge the energy from ambient sources present in our surroundings to cater to the energy needs of portable wearable electronics, are becoming more widespread because of their miniaturization and multifunctional characteristics. Triboelectric and piezoelectric nanogenerators are being explored to harvest electrical energy from the mechanical vibrations. Integration of these two effects to fabricate a hybrid nanogenerator can further enhance the output efficiency of the nanogenerator. Here, we have discussed the importance of 2D materials which plays an important role in the fabrication of nanogenerators because of their distinct characteristics, such as, flexibility, mechanical stability, nontoxicity, and biodegradability. This review mainly emphasizes the piezoelectric, triboelectric, and hybrid nanogenerator based on the 2D materials and their van der Waals heterostructure, as well as the effect of polymer-2D composite on the output performance of the nanogenerator.

Iron disorders and hepcidin.

Iron is an essential element due to its role in a wide variety of physiological processes. Iron homeostasis is crucial to prevent iron overload disorders as well as iron deficiency anemia. The liver synthesized peptide hormone hepcidin is a master regulator of systemic iron metabolism. Given its role in overall health, measurement of hepcidin can be used as a predictive marker in disease states. In addition, hepcidin-targeting drugs appear beneficial as therapeutic agents. This review emphasizes recent development on analytical techniques (immunochemical, mass spectrometry and biosensors) and therapeutic approaches (hepcidin agonists, stimulators and antagonists). These insights highlight hepcidin as a potential biomarker as well as an aid in the development of new drugs for iron disorders.

Electrochemical detection of hepcidin based on spiegelmer and MoS2NF-GNR@AuNPs as sensing platform.

Spiegelmers, mirror image L- RNA oligonucleotides, possesses high plasma stability and non-immunogenicity. Herein, a novel spiegelmer based impedimetric biosensor grafted with Au nanoparticles and molybdenum disulfide nanoflowers/graphene nanoribbons nanocomposite has been designed to detect hepcidin in spiked-in human serum sample. Firstly, molybdenum disulfide nanoflowers/graphene nanoribbons (MoS2NF-GNR) hybrid was drop-casted onto the FTO electrode followed by electro deposition of Au nanoparticles (AuNPs). Hepcidin specific thiolated spiegelmer was then immobilized on the MoS2NF-GNR@AuNPs for hepcidin detection. Electrochemical impedance spectroscopy was used to assess the performance of the sensing platform based on the variation of charge transfer resistance (ΔRct) relative to the Fe(CN)64-/3- electrochemical probe in the presence of hepcidin. The impedance signals were recorded at the frequency range of 10-1 to 105 Hz and potential was set as 0.18 V. Under optimized conditions, the limit of detection of spiegelmer based sensor for hepcidin was 0.173 pgmL-1 within a wide linear range of 0.005-10 ngmL-1. The biosensor possesses selectivity, acceptable reproducibility with RSD as 4.76% and stability for up to 20 days. The satisfactory recovery result (89.8-103.1 %) in human serum indicates that the sensor has applicability in clinical monitoring of hepcidin.

Voltammetric detection of vitamin D employing Au-MoS2 hybrid as immunosensing platform.

A voltammetric immunosensor based on molybdenum sulphide (MoS2) and gold nanoparticles (Au NPs) for the determination of 25-hydroxy vitamin D3 (25(OH)D3) is reported. Anti-vit D (Ab-25(OH)D3) was immobilized onto the cysteamine-modified MoS2 and Au NPs which were deposited onto a fluoride tin oxide (FTO) electrode (Ab/Cys/Au/MoS2/FTO). The MoS2 sheets were prepared by hydrothermal method followed by an in situ growth of Au film onto the MoS2/FTO surface. Self-assembled monolayer (SAM) of cysteamine was synthesized onto the Au/MoS2/FTO which acts as a linker to covalently bind Ab-25(OH)D3. The Ab-25(OH)D3-immobilized Cys/Au/MoS2/FTO was used to detect 25(OH)D3 using differential pulse voltammetry. The electrochemical system provided an anodic peak current at a potential of +0.21 V vs. Ag/AgCl (satd. KCl) of ferricyanide/ferrocyanide redox couple. The detection principle relies on the inhibition of electron transfer at the electrode surface owing to the hindrance caused by the formation of immune complex between Ab-25(OH)D3 and 25(OH)D3. The immunosensor shows linear response from 1 pg mL-1 to 100 ng mL-1 25(OH)D3 and a sensitivity of 189 µA [log (pg mL-1)]-1 cm-2 along with a low limit of detection (LOD) of 0.38 pg mL-1. The immunosensor is highly selective towards 25(OH)D3 and presented a long shelf life of 28 days. Also, the immunosensor exhibits satisfactory performance towards spiked human serum samples with recovery between 95.1 and 102% (RSD 1.15-3.22%).

Gold-silver core-shell nanoparticle-based impedimetric immunosensor for detection of iron homeostasis biomarker hepcidin.

An impedimetric immunosensor based on gold-silver core-shell nanoparticles for hepcidin detection is reported. The core-shell nanoparticles were prepared by seed-mediated method and characterized by dynamic light scattering, UV-Vis, XRD, field emission-scanning electron micrograph imaging, energy dispersive spectroscopy, and atomic force microscopy. The immunosensor was fabricated with core-shell nanoparticles and cysteamine employing covalent chemistry (amide bond formation) strategy for ensuring proper orientation of anti-hepcidin antibody on to the amine-functionalized nanomaterial decorated electrodes. The hepcidin detection principle was based on the variation of charge transfer resistance (ΔRct) relative to the Fe(CN)64-/3- electrochemical probe in the presence of the biomarker. The frequency range was 10-1 to 105 Hz at the scan rate of 10 mV s-1and a potential of 0.1 V. Based on the antigen-antibody interaction in 40 min at pH 7.0, a linear relationship between ΔRct and hepcidin concentration was obtained in the range 0.01 to 100 ng/mL with a detection limit of 0.857 pg/mL. Furthermore, the designed immunosensor had acceptable reproducibility, stability, selectivity, and reusability. It was successfully applied to the detection of hepcidin in spiked human serum samples and acceptable recovery (90-95.9%) was obtained. Graphical abstract Gold-silver core-shell nanoparticle-based impedimetric immunosensor for detection of iron homeostasis biomarker hepcidin. The study focuses on the detection of iron regulatory protein hepcidin using gold-silver core-shell nanoparticles. This immunosensor was fabricated with core-shell nanoparticles and cysteamine employing covalent chemistry (amide bond formation) strategy. The sensor was sensitive in the range from 0.01 to 100 ng/mL, with a detection limit of 0.857 pg/mL.

Electrochemical biosensor for miRNA-21 based on gold-platinum bimetallic nanoparticles coated 3-aminopropyltriethoxy silane.

We report an electrochemical biosensor based on gold platinum bimetallic nanoparticles (AuPtBNPs)/3-aminopropyltriethoxy silane (APTS) nanocomposite coated fluorine-doped tin oxide (FTO) as a biosensing platform for hybridization-based detection of miRNA-21. Field Emission-Scanning Electron Microscopy (FE-SEM), Fourier Transform Infrared Spectroscopy (FT-IR) and electrochemical measurements were carried out to ensure the successful construction of the biosensor. The amount of cDNA immobilized on electrode surface and hybridization time required for the miRNA-21 sensing were optimized. The biosensing platform showed detection limit of 0.63 fM with wide linear range i.e. 1 fM-100 nM for miRNA-21 detection. The biosensing strategy demonstrates a good recovery yield from 90.18% to 94.6% in serum samples. It offers good selectivity for its complementary miRNA compared to the non-complementary miRNAs. Other analytical features of the biosensor such as stability, reusability and reproducibility were also tested, providing appropriate results.

An electrochemical aptasensor for analysis of MUC1 using gold platinum bimetallic nanoparticles deposited carboxylated graphene oxide.

A simple electrochemical strategy has been designed for the analysis of MUC1 using electrodeposited gold platinum bimetallic nanoparticles (Au-PtBNPs) on the surface of carboxylated graphene oxide (CGO)/FTO electrode as a signal amplification platform. The carboxylic groups of CGO were activated with EDS-NHS linker and subsequently immobilized with streptavidin for further deposition of biotin labelled aptamer. All the modification steps were characterized by FE-SEM, EDS mapping, FT-IR, contact angle measurements and electrochemical methods. After incubating with target protein MUC1, the aptaelectrode produced some concentration dependent responses which were measured electrochemically by DPV assay. The prepared aptasensor exhibits wide linear range from 1 fM-100 nM with detection limit of 0.79 fM under optimal experimental conditions. The performance of this aptaelectrode was also evaluated showing good selectivity, storage stability (15 days), reproducibility and reusability (up to 3 times). Furthermore, the applicability of the aptasensor for spiked serum samples showed recovery range from 92% to 97%.

Novel Liposome Eencapsulated Guanosine Di Phosphate based Therapeutic Target against Anemia of Inflammation.

Hepcidin, master regulator of iron homeostasis, causes anemia under infectious and inflammatory conditions by reducing intestinal absorption of iron with decreased release of iron from macrophages and liver despite adequate iron stores leading to Anemia of Inflammation (AI). Many therapeutic trials have been carried out but none have been effective due to its adverse effects. In present study, we discover that Guanosine 5'-diphosphate (GDP) encapsulated in lipid vesicle (NH+) was found to inhibit NF-ҝB activation by limiting phosphorylation and degradation of IҝBα, thus, attenuating IL-6 secretion from macrophage cells. Moreover, the suppressed IL-6 levels down regulated JAK2/STAT3 pathway with decrease inflammation-mediated Hamp mRNA transcription (HepG2) and increase iron absorption (Caco2) in HepG2/Caco2 co-culture model. Analogous results were obtained in acute and chronic AI mice model thus, correcting haemoglobin level. These results proved NH + GDP as novel therapeutic agent to overcome limitations and suggests it as potential drug to ameliorate AI.