Nanoparticles mediated folic acid enrichment.

Folate is an essential component of many metabolic processes, and folate deficiency is known to cause various disorders. Folate and folic acid, a synthetic and chemically stable form of folate, enriched diet are typically used to overcome this deficiency. Folic acid and folate however, are susceptible to harsh environment and folates enrichment using nanoparticles is an intensively studied strategy in food industry. This review highlights the current methods and types of matrices utilized to develop folic acid/folate carrying nanoparticles. The folic acid/folate loaded nanoparticles prevent cargo degradation during gut absorption and under harsh food processing conditions including, high temperatures, UV light, and autoclaving. The data demonstrates that nanofortifcation of folates using proteins and biopolymers effectively enhances the bioavailability of the cargo. The encapsulation of folic acid in biopolymers by emulsion, spray drying and ionic gelation represent simplistic methods that can be easily scaled up with applications in food industry.

Secondary Structure Stabilization of Macrocyclic Antimicrobial Peptides via Cross-Link Swapping.

Lactam cross-links have been employed to stabilize the helical secondary structure and enhance the activity and physiological stability of antimicrobial peptides; however, stabilization of ß-sheets via lactamization has not been observed. In the present study, lactams between the side chains of C- and N-terminal residues have been used to stabilize the ß-sheet conformation in a short ten-residue analogue of chicken angiogenin-4. Designed using a combination of molecular dynamics simulations and Markov state models, the lactam cross-linked peptides are shown to adopt stabilized ß-sheet conformations consistent with simulated structures. Replacement of the peptide side-chain Cys-Cys disulfide by a lactam cross-link enhanced the broad-spectrum antibacterial activity compared to the parent peptide and exhibited greater propensity to induce proinflammatory activity in macrophages. The combination of molecular simulations and conformational and biological analyses of the synthetic peptides provides a useful paradigm for the rational design of therapeutically active peptides with constrained ß-sheet structures.

Clinical Advances in Triple Negative Breast Cancer Treatment: Focus on Poly (L-lactide-coglycolide) Nanoparticles.

Triple negative breast cancer (TNBC) is the most aggressive type of breast cancer and is associated with high probability of metastasis and poor prognosis. Chemotherapeutics and surgery remain the most common options for TNBC patients; however, chemotherapeutic resistance and relapse of tumors limit the progression free survival and patient life span. This review provides an overview of recent chemotherapeutics that are in clinical trial, and the combination of drugs that are being investigated to overcome the drug resistance and to improve patient survival in different molecular subtypes of TNBCs. Nanotherapeutics have emerged as a promising platform for TNBC treatment and aim to improve the selectivity and solubility of drugs, reduce systemic side effects, and overcome multi-drug resistance. The study explores the role of nanoparticles for TNBC treatment and summarizes the types of nanoparticles that are in clinical trials. Poly(L-lactide-co-glycolide) (PLGA) is the most studied polymeric carrier for drug delivery and for TNBC treatment in research and in clinics. This review is about providing recent advancements in PLGA nanotherapeutic formulations and their application to help treat TNBC. Some background on current chemotherapies and pathway inhibitors is provided so that the readers are aware of what is currently considered for TNBC. Some of the pathway inhibitors may also be of importance for nanotherapeutics development. SIGNIFICANCE STATEMENT: This minireview summarizes the progress on chemotherapeutics and nanoparticle delivery for treatment of TNBC and specifically highlights the lead compounds that are in clinical trials.

Chemotherapeutics-Loaded Poly(Dopamine) Core-Shell Nanoparticles for Breast Cancer Treatment.

Chemophotothermal therapy is an emerging treatment of metastatic and drug-resistant cancer anomalies. Among various photothermal agents tested, poly(dopamine) provides an excellent biocompatible alternative that can be used to develop novel drug delivery carriers for cancer treatment. This study explores the synthesis of starch-encapsulated, poly(dopamine)-coated core-shell nanoparticles in a one-pot synthesis approach and by surfactant-free approach. The nanoparticles produced are embellished with polymeric stealth coatings and are tested for their physiologic stability, photothermal properties, and drug delivery in metastatic triple-negative breast cancer cell (TNBC) lines. Our results indicate that stealth polymer-coated nanoparticles exhibit superior colloidal stability under physiologic conditions, and are excellent photothermal agents, as determined by the increase in temperature of solution in the presence of nanoparticles, upon laser irradiation. The chemotherapeutic drug-loaded nanoparticles also showed concentration-dependent toxicities in TNBC and in a brain metastatic cell line. SIGNIFICANCE STATEMENT: This study develops, for the first time, biocompatible core-shell nanoparticles in a template-free approach that can serve as a drug delivery carrier and as photothermal agents for cancer treatment.

A review: Hydrochar as potential adsorbents for wastewater treatment and CO2 adsorption.

To valorize the biomass and organic waste, hydrothermal carbonization (HTC) stands out as a highly efficient and promising pathway given its intrinsic advantages over other thermochemical processes. Hydrochar, as the main product obtained from HTC, is widely applied as a fuel source and soil conditioner. Aside from these applications, hydrochar can be either directly used or modified as bio-adsorbents for environmental remediation. This potential arises from its tunable surface chemistry and its suitability to act as a precursor for activated or engineered carbon. In view of the importance of this topic, this review offers a thorough examination of the research progress for using hydrochar and its modified forms to remove organic dyes (cationic and anionic dyes), heavy metals, herbicides/pesticides, pharmaceuticals, and CO2. The review also sheds light on the fundamental chemistry involved in HTC of biomass and the major analytical techniques applied for understanding surface chemistry of hydrochar and modified hydrochar. The knowledge gaps and potential hurdles are identified to highlight the challenges and prospects of this research field with a summary of the key findings from this review. Overall, this article provides valuable insights and directives and pinpoints the areas meriting further investigation in the application potential of hydrochar in wastewater management and CO2 capture.

Enhanced Cryopreservation Efficacies of Ice Recrystallization Inhibiting Nanogels.

Development of new cryopreservation technologies holds significant potential to revolutionize the fields of cell culture, tissue engineering, assisted reproduction, and transfusion medicine. The current gold standard small-cell permeating cryopreservation agents (CPAs) demonstrate promising cryopreservation efficacies but are cytotoxic and immunogenic at the concentrations required for cryopreservation applications. In comparison, new cell impermeable CPAs of nanodimensions demonstrate outstanding potential to overcome the drawbacks of existing CPAs. In this study, we report the synthesis of vitamin B5 analogous methacrylamide (B5AMA)-incorporated nanogels as a potential solution to address the commonly observed limitations of existing CPAs. The stimuli-responsive poly(B5AMA) nanogels prepared by radical polymerization demonstrated significant ice recrystallization inhibition efficacies and showed either superior or comparable cryopreservation efficacies compared to the traditional cryoprotectant DMSO/glycerol in both eukaryotic and prokaryotic cells.

History and Clinical Development of Nanomedicines, Nanostructure, and Nanoscale Sciences.

Context: Extraordinary advances in the fields of polymer nanoparticle (nano) drug technology, nanomedicines, nanostructures, and nanoscale sciences have played a key role in the healthcare system. New nanodrug complexes have exceptional pharmacological properties with large surface areas that encourage a formulated medication to distribute, absorb, and produce the desired clinical effects. Objective: The current study aimed to review the latest development in the field of nanodrug particles, theranostic, use of noninvasive techniques, and enhancement of retention of nano-theranostic formulations. That helps to develop the innovative pharmaceutical dosage forms. Setting: The latest published data extracted from search engines PubMed, Scopus, Medline, Wolfram Alpha, BASE, Science.gov, Semantic Scholar, Education Resources Information Center, Microsoft Academic, ResearchGate, RefSeek, WorldWideScience, arXiv, Microsoft Academic Search, Google Books, JSTOR, Scirus, Social Science Research Network, Bioline International, SciELO, MetaCrawler, PLOS One, Google Scholar, and Infotopia. Design: The metadata of clinical trials, retrospective, prospective and case control studies collected from the peer review research/ review articles. The aforesaid search engines used to explore the latest information published in ≤200 research studies. the key words Nanomedicines, nanostructure, nanoscale sciences and clinical development run into the system to obtain more specific information. The final data was analyzed, interpreted and narrated for his study. Result: The precisely use of nanodrug for targeted disease produced considerable clinical results. Particularly the designed therapeutic nanoparticle formulations help to reduce the excretion, prolong blood circulation to increase accumulation at a targeted site and increase the therapeutic effects. Conclusions: The nanodrug complexes are successfully translated into several modern medications. The new and innovative nanodrug can potentially be used precisely and correctly to diagnose and treat the terminally ill patients. However, the developed nanodrug complexes, whether they are carriers or therapeutic agents, need thorough physiochemical, pharmacological, and immunological characterization before actual use in clinical practice in different human population of the world.

Metastatic Breast Cancer: Review of Emerging Nanotherapeutics.

Metastases of breast cancer (BC) are often referred to as stage IV breast cancer due to their severity and high rate of mortality. The median survival time of patients with metastatic BC is reduced to 3 years. Currently, the treatment regimens for metastatic BC are similar to the primary cancer therapeutics and are limited to conventional chemotherapy, immunotherapy, radiotherapy, and surgery. However, metastatic BC shows organ-specific complex tumor cell heterogeneity, plasticity, and a distinct tumor microenvironment, leading to therapeutic failure. This issue can be successfully addressed by combining current cancer therapies with nanotechnology. The applications of nanotherapeutics for both primary and metastatic BC treatments are developing rapidly, and new ideas and technologies are being discovered. Several recent reviews covered the advancement of nanotherapeutics for primary BC, while also discussing certain aspects of treatments for metastatic BC. This review provides comprehensive details on the recent advancement and future prospects of nanotherapeutics designed for metastatic BC treatment, in the context of the pathological state of the disease. Furthermore, possible combinations of current treatment with nanotechnology are discussed, and their potential for future transitions in clinical settings is explored.

Elucidating the Role of Optical Activity of Polymers in Protein-Polymer Interactions.

Proteins are biomolecules with potential applications in agriculture, food sciences, pharmaceutics, biotechnology, and drug delivery. Interactions of hydrophilic and biocompatible polymers with proteins may impart proteolytic stability, improving the therapeutic effects of biomolecules and also acting as excipients for the prolonged storage of proteins under harsh conditions. The interactions of hydrophilic and stealth polymers such as poly(ethylene glycol), poly(trehalose), and zwitterionic polymers with various proteins are well studied. This study evaluates the molecular interactions of hydrophilic and optically active poly(vitamin B5 analogous methacrylamide) (poly(B5AMA)) with model proteins by fluorescence spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and circular dichroism (CD) spectroscopy analysis. The optically active hydrophilic polymers prepared using chiral monomers of R-(+)- and S-(-)-B5AMA by the photo-iniferter reversible addition fragmentation chain transfer (RAFT) polymerization showed concentration-dependent weak interactions of the polymers with bovine serum albumin and lysozyme proteins. Poly(B5AMA) also exhibited a concentration-dependent protein stabilizing effect at elevated temperatures, and no effect of the stereoisomers of polymers on protein thermal stability was observed. NMR analysis, however, showed poly(B5AMA) stereoisomer-dependent changes in the secondary structure of proteins.

Evaluation of Biological Activities and Medicinal Properties of Honey Drops and Honey Lozenges.

Raw honey naturally possesses a number of health benefits that are imbued by its components, including phenolics acids, flavonoids, enzymes, sugars, and organic acids. Processing of raw honey at high temperatures, often leads to a loss of biological activity and active ingredients, hence, reducing the medicinal benefits of processed honey samples. This study describes that the processing of raw honey into honey-based candies slightly changed the physicochemical properties of raw honey, as was observed by the loss of diastase activity and reduction in hydrogen peroxide content in honey-based candies. However, the overall health benefits of honey-based candies were maintained. The processing of honey into candies (lozenges and drops) maintained antibacterial and anti-inflammatory activities of honey candies relative to the raw honey samples.

Enzyme-Linked Immunosorbent Assay (ELISA).

Enzyme-linked immunosorbent assay (ELISA) is one of the most specific and straightforward assays for detecting biomolecules in research and clinics. With advances in analytical methods, ELISA assay has been constantly optimized to improve its sensitivity, and different types of ELISA are now available to detect various biomarkers. This chapter provides an overall summary of the basic principle of ELISA, discusses different components of ELISA assay, and clearly outline protocols for different types of ELISA assays, including direct, indirect, sandwich, competitive, and nanoparticle-based ELISA.

Size and macromolecule stabilizer-dependent performance of gold colloids in immuno-PCR.

Gold nanoparticles (GNPs) are well-documented for their size and surface chemistry-dependent electronic and optical properties that are extensively utilized to develop highly sensitive immunoassays. GNP-based immuno-polymerase chain reaction (immuno-PCR) is especially interesting due to the facile loading of biomolecules on the surface of GNP probes and has been utilized to develop analyte-specific assays. In this study, the role of size and surface chemistry of GNPs is explored in detail to develop a highly sensitive and reproducible immuno-PCR assay for specific detection of biotinylated analytes. Our results indicate that smaller-sized gold nanoparticles outperform the larger ones in terms of their sensitivity in immuno-PCR assay and show superior loading of proteins and oligonucleotides on the surface of nanoparticles. Furthermore, the role of different macromolecular stabilizers (such as polyethylene glycol (PEG), bovine serum albumin (BSA), and PEGylated BSA) was compared to optimize the loading of biomolecules and to improve the signal-to-noise ratio of GNP probes. mPEG-BSA-functionalized GNP probes of 15 nm were found to be highly sensitive at low concentrations of analytes and significantly (~ 30 fold) improve the limit of detection of analytes in comparison with ELISA assay.

Antibacterial activities of physiologically stable, self-assembled peptide nanoparticles.

In this study, we report that host defense protein-derived ten amino acid long disulfide-linked peptides self-assemble in the form of ß-sheets and ß-turns, and exhibit concentration-dependent self-assembly in the form of nanospheres, termed as disulfide linked nanospheres (DSNs). As expected, bare DSNs are prone to aggregation in ionic solutions and in the presence of serum proteins. To yield physiologically stable self-assembled peptide-based materials, DSNs are stabilized in the form of supramolecular assemblies using ß-cyclodextrins (ß-CD) and fucoidan, as delivery carriers. The inclusion complexes of DSNs with ß-CD (ß-CD-DSN) and electrostatic complexation of fucoidan with DSNs (FC-DSN) stabilizes the secondary structure of DSNs. Comparison of ß-CD-DSNs with FC-DSNs reveals that inclusion complexes of DSNs formed in the presence of ß-CD are highly stable under physiological conditions, show high cellular uptake, exhibit bacterial flocculation, and enhance antibacterial efficacies of DSNs in a range of Gram-positive and Gram-negative bacteria.

Bacterial-Specific Aggregation and Killing of Immunomodulatory Host Defense Peptides.

This study involves the design and development of disulfide bridge-linked antimicrobial peptides using the host defense protein Angiogenin 4 (chAng4) as a template. The mini peptides derived from chAng4 (mCA4s) were evaluated for their antibacterial efficacies in various pathogenic bacterial strains, and the role of the oxidation state of thiols in the peptide sequence and its implication on antibacterial properties were explored. A remarkable property of these synthetic mCA4 peptides is their capability to flocculate bacteria and mediate bacterial-specific killing, in the absence of any other external stimulus. mCA4s were further evaluated for their cellular uptake, hemolytic activities, toxicities, and immunomodulatory activities in different eukaryotic cell lines. The results indicate that disulfide bridge-containing cationic amphipathic peptides show superior antibacterial efficacies, are nontoxic and nonhemolytic, and mediate bacterial flocculation and killing, in the absence of external stimuli.

Applications of gold nanoparticles in ELISA, PCR, and immuno-PCR assays: A review.

Development of state-of-the-art assays for sensitive and specific detection of disease biomarkers has received significant interest for early detection and prevention of various diseases. Enzyme Linked Immunosorbent assays (ELISA) and Polymerase Chain Reaction (PCR) are two examples of proteins and nucleic acid detection assays respectively, which have been widely used for the sensitive detection of target analytes in biological fluids. Recently, immuno-PCR has emerged as a sensitive detection method, where high specificity of sandwich ELISA assays is combined with high sensitivity of PCR for trace detection of biomarkers. However, inherent disadvantages of immuno-PCR assays limit their application as rapid and sensitive detection method in clinical settings. With advances in nanomaterials, nanoparticles-based immunoassays have been widely used to improve the sensitivity and simplicity of traditional immunoassays. Owing to facile synthesis, surface functionalization, and superior optical and electronic properties, gold nanoparticles have been at the forefront of sensing and detection technologies and have been extensively studied to improve the efficacies of immunoassays. This review provides a brief history of immuno-PCR assays and specifically focuses on the role of gold nanoparticles to improve the sensitivity and specificity of ELISA, PCR and immuno-PCR assays.

Effect of magnetic field alignment of cellulose nanocrystals in starch nanocomposites: Physicochemical and mechanical properties.

The magnetic field (MF) induced alignment of cellulose nanocrystals (CNC) within a starch matrix is investigated and its effect on the physicochemical and mechanical properties of the nanocomposites are discussed in the paper. Two different kinds of CNC i.e. plant-CNC and tunicate-CNC and its hybrid combination are studied to understand the effect of aspect ratio of CNC on the properties of nanocomposite. Nanocomposites with tunicate sourced CNC showed higher tensile strength and modulus, and lower water vapor permeability as compared to plant sourced CNC. These properties are higher for nanocomposites prepared under MF. The modulus of starch nanocomposites increased from 0.26 GPa and 0.32 GPa to 0.38 GPa and 0.44 GPa, respectively for plant-CNC and tunicate-CNC when exposed to MF. The improved orientation and alignment of CNC in presence of MF is further supported by Raman and scanning electron micrographs studies.

Identification, tissue characterization, and innate immune role of Angiogenin-4 expression in young broiler chickens.

Intestinal epithelial cells are major producers of antimicrobial proteins, which play an important role in innate immunity. In addition to defensins, the Ribonuclease A superfamily includes important antimicrobial proteins involved in host-defense mechanisms in vertebrates. Angiogenin-4 (Ang4), a member of this RNase superfamily, has been demonstrated to be secreted by Paneth cells in mice. We have successfully cloned and characterized a new chicken gene (chAng4), found for the first time in a nonmammalian species, from intestinal epithelial and lymphoid cells. Characterization of chAng4 revealed 99% nucleotide and 97% amino acid sequence homology to mouse Ang4. Similar functional regions were identified, suggesting a role in innate immunity and regulation of gut microbiota. Furthermore, the mRNA expression pattern of chAng4 was studied in broilers in the presence or absence of beneficial bacteria (probiotics) and organic acids. The results showed that one-day-old chickens expressed low levels of Ang4 in almost all the evaluated tissues (crop, proventriculus, duodenum, jejunum, ileum, and cecal tonsils), except in the bursa of Fabricius that presented the highest expression level. The addition of probiotics and organic acids for either 7 or 14 consecutive days demonstrated a direct effect of probiotics and organic acids on chAng4 expression; moreover, broilers receiving probiotics and organic acids for only 7 D showed higher levels of chAng4 expression compared with those treated for 14 D. Broilers without treatment had a constant high level of expression in cecal tonsils and bursa. In conclusion, we were able to identify and characterize a new antimicrobial gene in chickens (chAng4) throughout the gastrointestinal tract. chAng4 mRNA gene expression was associated with the presence of naturally occurring and supplemented (probiotic) bacteria. The encoded protein might have a potential bactericidal effect against intestinal nonpathogenic and pathogenic microbes, modulating the intestinal microbiota and the innate immunity, and thereby may help minimize the use of antibiotics in poultry feed.

Low-temperature solvent-based 3D printing of PLGA: a parametric printability study.

In this paper, a novel low-temperature 3 D printing technique is introduced and characterized through a parametric printability study to fabricate poly-lactic-co-glycolic acid (PLGA) constructs using methyl ethyl ketone (MEK) as a solvent. The effects of varying concentrations of PLGA in MEK solvent, lactic to glycolic ratio of PLGA, the molecular weight of PLGA, and the scaling of PLGA constructs on the printability are investigated. PLGA concentrations of higher than 80% w/v, lactic to glycolic ratio more than 75%, molecular weight more than 100 kDa, and printing through nozzles smaller than 0.96 mm internal diameter are recommended for 3 D printing of PLGA constructs with high shape fidelity. Ultimately, a vacuum drying solvent removal process is implemented, and Proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy is used to confirm complete removal of the solvent from PLGA constructs. The results of this study can be used for the development of drug-eluting implants.

Elucidating the Role of Thermal Flexibility of Hydrogels in Protein Refolding.

Synthetic chaperones are stimuli-responsive materials that facilitate the refolding of denatured proteins in their native form and release refolded proteins in solution in the presence of external stimuli. Thermoresponsive hydrogels are a class of synthetic chaperones that require heat as an external stimulus to refold the denatured proteins into their biologically active conformations; however, the mechanism by which these hydrogels participate in protein refolding mechanism remains unclear. In this study, we explore the role of physical and structural changes in the hydrogel matrix that may participate in protein refolding efficacies of thermally responsive poly(vitamin B5 analogous methacrylamide) poly(B5AMA) hydrogels. Poly(B5AMA) hydrogels of different net charges, hydrophobicity, and cross-linking densities are synthesized by radical polymerization method and are evaluated for the restoration of enzymatic activity of thermally denatured enzymes (lysozyme and carbonic anhydrase) as a function of temperature and time and for the presence of residual water in the hydrogel architecture. The hydrogels with promising protein renaturation efficacies are further evaluated for their interactions with denatured proteins, and the role of thermal flexibility of the hydrogel matrix in protein refolding capabilities is elucidated.