Peptide-Carbon Quantum Dots conjugate, Derived from Human Retinoic Acid Receptor Responder Protein 2, against Antibiotic-Resistant Gram Positive and Gram Negative Pathogenic Bacteria

Antibiotic-resistant bacterial infections have become global issues for public health, which increases the utter need to develop alternatives to antibiotics. Here, the HSER (Homo sapiens retinoic acid receptor) peptide was designed from retinoic acid receptor responder protein 2 of Homo sapiens, and was conjugated with synthesized CQDs (carbon quantum dots) for enhanced antibacterial activity in combination, as individually they are not highly effective. The HSER-CQDs were characterized using spectrophotometer, HPLC coupled with electrospray-ionization quadrupole time-of-flight mass spectrometer (ESI-qTOF) mass spectrometer, zeta potential, zeta size, and FTIR. Thereafter, the antibacterial activity against Vancomycin-Resistant Staphylococcus aureus (VRSA) and Escherichia coli (carbapenem resistant) was studied using growth curve analysis, further supported by microscopic images showing the presence of cell debris and dead bacterial cells. The antibacterial mechanism of HSER-CQDs was observed to be via cell wall disruption and also interaction with gDNA (genomic DNA). Finally, toxicity test against normal human epithelial cells showed no toxicity, confirmed by microscopic analysis. Thus, the HSER-CQDs conjugate, having high stability and low toxicity with prominent antibacterial activity, can be used as a potential antibacterial agent.O

Maghemite particles for spermidine separation

We report the optimal conditions for the separation of spermidine from different types of samples, for example blood or cancer cells and its subsequent determination by ion-exchange liquid chromatography (IEC) with UV-VIS detector. Here in, we synthesized paramagnetic particles able to isolate and immobilize spermidine from blood of patients with cancer or cancer cells and thus preconcentrate it for analysis. Dowex surface was covered by nanomaghemite (-Fe2O3) or maghemite particles surface was modified by chitosan and sulfoxyethyl cellulose. The best separation properties showed Dowex microparticles. The paramagnetic particles can be used in the future for isolation of spermidine from real samples and diagnosis of cancer

Characterization and in vitro analysis of probiotic-derived peptides against multi drug resistance bacterial infections

An inexorable switch from antibiotics has become a major desideratum to overcome antibiotic resistance. Bacteriocin fromLactobacillus casei, a cardinal probiotic was used to design novel antibacterial peptides named as Probiotic Bacteriocin Derived and Modified (PBDM) peptides (PBDM1: YKWFAHLIKGLC and PBDM2: YKWFRHLIKKLC). The loop-shaped 3D structure of peptides was characterizedin silicovia molecular dynamics simulation as well as biophysically via spectroscopic methods. Thereafter,in vitroresults against multidrug resistant bacterial strains and hospital samples demonstrated the strong antimicrobial activity of PBDM peptides. Further,in vivostudies with PBDM peptides showed downright recovery of balb/c mice from Vancomycin ResistantStaphylococcus aureus(VRSA) infection to its healthy condition. Thereafter,in vitrostudy with human epithelial cells showed no significant cytotoxic effects with high biocompatibility and good hemocompatibility. In conclusion, PBDM peptides displayed significant antibacterial activity against certain drug resistant bacteria which cause infections in human beings. Future analysis are required to unveil its mechanism of action in order to execute it as an alternative to antibiotics

Nanocomposite furcellaran films - The influence of nanofillers on functional properties of furcellaran films and effect on linseed oil preservation

Nanocomposite films that were based on furcellaran (FUR) and nanofillers (carbon quantum dots (CQDs), maghemite nanoparticles (MAN), and graphene oxide (GO)) were obtained by the casting method. The microstructure, as well as the structural, physical, mechanical, antimicrobial, and antioxidant properties of the films was investigated. The incorporation of MAN and GO remarkably increased the tensile strength of furcellaran films. However, the water content, solubility, and elongation at break were significantly reduced by the addition of the nanofillers. Moreover, furcellaran films containing the nanofillers exhibited potent free radical scavenging ability. FUR films with CQDs showed an inhibitory effect on the growth of Staphylococcus aureus and Escherichia coli. The nanocomposite films were used to cover transparent glass containers to study the potential UV-blocking properties in an oil oxidation test and compare with tinted glass. The samples were irradiated for 30 min. with UV-B and then analyzed for oxidation markers (peroxide value, free fatty acids, malondialdehyde content, and degradation of carotenoids). The test showed that covering the transparent glass with MAN films was as effective in inhibiting the oxidation as the use of tinted glass, while the GO and CQDs films did not inhibit oxidation. It can be concluded that the active nanocomposite films can be used as a desirable material for food packaging

Norepinephrine Transporter-Derived Homing Peptides Enable Rapid Endocytosis of Drug Delivery Nanovehicles into Neuroblastoma Cells

Background: Currently, the diagnosis and treatment of neuroblastomas-the most frequent solid tumors in children-exploit the norepinephrine transporter (hNET) via radiolabeled norepinephrine analogs. We aim to develop a nanomedicine-based strategy towards precision therapy by targeting hNET cell-surface protein with hNET-derived homing peptides. Results: The peptides (seq.GASNGINAYL and SLWERLAYGI) were shown to bind high-resolution homology models of hNET in silico. In particular, one unique binding site has marked the sequence and structural similarities of both peptides, while most of the contribution to the interaction was attributed to the electrostatic energy of Asn and Arg (< - 228 kJ/mol). The peptides were comprehensively characterized by computational and spectroscopic methods showing similar to 21% beta-sheets/aggregation for GASNGINAYL and similar to 27% alpha-helix for SLWERLAYGI. After decorating 12-nm ferritin-based nanovehicles with cysteinated peptides, both peptides exhibited high potential for use in actively targeted neuroblastoma nanotherapy with exceptional in vitro biocompatibility and stability, showing minor yet distinct influences of the peptides on the global expression profiles. Upon binding to hNET with fast binding kinetics, GASNGINAYLC peptides enabled rapid endocytosis of ferritins into neuroblastoma cells, leading to apoptosis due to increased selective cytotoxicity of transported payload ellipticine. Peptide-coated nanovehicles significantly showed higher levels of early apoptosis after 6 h than non-coated nanovehicles (11% and 7.3%, respectively). Furthermore, targeting with the GASNGINAYLC peptide led to significantly higher degree of late apoptosis compared to the SLW-ERLAYGIC peptide (9.3% and 4.4%, respectively). These findings were supported by increased formation of reactive oxygen species, down-regulation of survivin and Bcl-2 and up-regulated p53. Conclusion: This novel homing nanovehicle employing GASNGINAYLC peptide was shown to induce rapid endocytosis of ellipticine-loaded ferritins into neuroblastoma cells in selective fashion and with successful payload. Future homing peptide development via lead optimization and functional analysis can pave the way towards efficient peptide-based active delivery of nanomedicines to neuroblastoma cells

Zinc phosphate-based nanoparticles as a novel antibacterial agent: in vivo study on rats after dietary exposure

Background: Development of new nanomaterials that inhibit or kill bacteria is an important and timely research topic. For example, financial losses due to infectious diseases, such as diarrhea, are a major concern in livestock productions around the world. Antimicrobial nanoparticles (NPs) represent a promising alternative to antibiotics and may lower antibiotic use and consequently spread of antibiotic resistance traits among bacteria, including pathogens. Results: Four formulations of zinc nanoparticles (ZnA, ZnB, ZnC, and ZnD) based on phosphates with spherical (ZnA, ZnB) or irregular (ZnC, ZnD) morphology were prepared. The highest in vitro inhibitory effect of our NPs was observed against Staphylococcus aureus (inhibitory concentration values, IC50, ranged from 0.5 to 1.6mmol/L), followed by Escherichia coli (IC50 0.8-1.5mmol/L). In contrast, methicillin resistant S. aureus (IC50 1.2-4.7mmol/L) was least affected and this was similar to inhibitory patterns of commercial ZnO-based NPs and ZnO. After the successful in vitro testing, the in vivo study with rats based on dietary supplementation with zinc NPs was conducted. Four groups of rats were treated by 2,000mg Zn/kg diet of ZnA, ZnB, ZnC, and ZnD, for comparison two groups were supplemented by 2,000mg Zn/kg diet of ZnO-N and ZnO, and one group (control) was fed only by basal diet. The significantly higher (P<0.05) Zn level in liver and kidney of all treated groups was found, nevertheless ZnNPs did not greatly influence antioxidant status of rats. However, the total aerobic and coliform bacterial population in rat feces significantly decreased (P<0.05) in all zinc groups after 30d of the treatment. Furthermore, when compared to the ZnO group, ZnA and ZnC nanoparticles reduced coliforms significantly more (P<0.05). Conclusions: Our results demonstrate that phosphate-based zinc nanoparticles have the potential to act as antibiotic agents