Glycol Molecules Research Articles

Optimization of the Preparation and Characterization of Tannylated-Albumin Nanoagents

We optimized the preparation of tannylated-human serum albumin (TA-HSA) nanoagents including indocyanine green (ICG) and lobeglitazone (Lobe)-loaded complexes by simple mixing and characterized them. We set the optimal pH at 5 and the optimal weight ratio of [TA]/[HSA] at 1.5 when considering the redispersion of the prepared suspensions in PBS (pH 7.4) and incubation at 37 ·C for the preparation of ICG and/or Lobe-loaded TA-HSA complexes. The immobilization of methoxy polyethylene glycol (mPEG) molecules on TA-HSA-ICG complexes significantly reduces the mean and Z-average sizes of these complexes from the microscale to the nanoscale. Moreover, the use of ICG increases the drug loading efficiency when preparing mPEG-TA-HSA-ICG/Lobe.

Hydrolytic stability of PEG-grafted γ-alumina membranes: Alkoxysilane vs phosphonic acid linking groups

Abstract Small polyethylene glycol (PEG) molecules were grafted on ceramic γ-alumina membranes, by making use of organo-alkoxysilanes or organo-phosphonic acids as linking groups. It was proven by FTIR that the short PEG brushes are chemically grafted into the pores of a 5 nm γ-alumina mesoporous support, which results in a decrease of the pore diameter as measured by cyclohexane permporometry (reduction of 2.1 nm). The stability of these PEG-grafted membranes was investigated in water for 216 h. Permeability and liquid state 1H NMR were used to show that PEG-modified membranes with an alkoxysilane linking group degrade rapidly during exposure to water. On the contrary, the phosphonic acid linking group remained grafted on γ-alumina supports for at least 216 h in water. In conclusion, this work shows a promising and simple method for the fabrication in a green solvent (water) of hydrophilic organically-modified ceramic membranes, which can be successfully applied for wastewater treatment.

Polyethylene glycol-mediated blocking and monolayer morphology of an electrochemical aptasensor for malaria biomarker detection in human serum

Better approaches are critically needed for in situ point-of-care diagnostic biosensors that enable primary care physicians, or even individual patients, to directly analyze biological fluids without complicated sample pretreatments. Additional purification steps consume time, consume reagents, often require other equipment, and can introduce false-negative results. Biosensors have been modified with blocking molecules to reduce biofouling; however, the effectiveness relies on their chemical composition and morphology. Here, we used a polyethylene glycol film to suppress unspecific binding from human serum on an electrochemical malaria aptasensor. A detailed study of the variation of the chemical and morphological composition of the aptamer/polyethylene glycol mixed monolayer as a function of incubation time was conducted. Higher resistance to matrix biofouling was found for polyethylene glycol than for hydrophobic alkanethiol films. The best sensor performance was observed for intermediate polyethylene glycol immobilization times. With prolonged incubation, phase separation of aptamer, and polyethylene glycol molecules locally increased the aptamer density and thereby diminished the analyte binding capability. Remarkably, polyethylene glycols do not affect the aptasensor sensitivity but enhance the complex matrix tolerance, the dynamic range, and the limit of detection. Careful tuning of the blocking molecule immobilization is crucial to achieving high aptasensor performance and biofouling resistance.

Upconversion Nanoparticle-Based Organosilica-Micellar Hybrid Nanoplatforms for Redox-Responsive Chemotherapy and NIR-Mediated Photodynamic Therapy.

Upconversion nanoparticles (UCNPs) can convert near-infrared light (NIR, 980 or 808 nm) to ultraviolet (UV) or visible light, which can be widely used to improve tissue penetration depth in photodynamic therapy (PDT). Herein, we develop a kind of UCNP-based organosilica-micellar hybrid nanoplatform for redox-responsive chemotherapy and NIR-mediated PDT. The nanoplatform was constructed by the self-assembly of block copolymers polystyrene-b-poly (acrylic acid) and oil-soluble UCNPs in the oil/water system and the subsequent organosilica coating with 3-mercaptopropyltrimethoxysilane molecules. To endow the nanosystem with more stability in biological media, polyethylene glycol molecules were further modified via the Michael addition reaction. As a promising nanocarrier, chlorin e6 (Ce6) and doxorubicin (DOX) molecules were loaded into the hydrophobic core and the disulfide-doped organosilica shell, respectively. With endocytosis by SMMC-7721 tumor cells, the Ce6 and DOX coloaded nanosystem was activated by UCNPs through luminescence resonance energy transfer under the irradiation of 808 nm laser, thus generating cytotoxic 1O2 for NIR-mediated PDT. Meanwhile, DOX was selectively released because of the redox-responsive biodegradation of the disulfide-doped organosilica shell in the glutathione over-expressed SMMC-7721 tumor cells. Based on these, the chemotherapy/PDT combination toxic feature of the multifunctional nanosystem was further demonstrated in the DOX-resistant MCF-7 tumor cells. On the other hand, the Ce6 and DOX coloaded nanosystem exhibited negligible toxicity to the normal 3T3 cell because of the protective effects of organosilica coating. We envision that the resultant hybrid nanoplatform provides us a promising nanocarrier for the combination therapy of redox-responsive safe chemotherapy and efficient NIR-mediated PDT.

Temperature-Dependent Supramolecular Isomeric Zn(II)-Metal–Organic Frameworks and Their Guest Exchange

A pair of three-dimensional metal–organic framework supramolecular isomers (1a and 2a) prepared from the solvothermal reactions of Zn(NO3)2·4H2O, 1,4-bis(4-pyridyl)piperazine (bpp), and 4,4′-oxybis(benzoic acid) (H2obc) in different temperatures was structurally elucidated, and a series of guest exchanges on these isomers were performed without the loss of single crystallinity. At 110 and 130 °C in DMF/H2O, an 8-fold [4 + 4] interpenetrated coordination polymer {[Zn(bpp)(obc)]·3H2O}n (1a) with sra topology and a self-penetrated coordination polymer {[Zn3(bpp)3(obc)3]·2DMF·4H2O}n (2a) with a new topology were isolated, respectively. In the guest-exchange experiments, water molecules in isomer 1a were displaced by acetone and ethylene glycol molecules, while dimethylformamide molecules in isomer 2a were replaced by acetone and ethylene glycol as well as bulkier diethylene glycol due to its larger void. Photoluminescence properties of two isomers and their guest-exchanged products were also measured and discussed.

Competition between intermolecular forces of adhesion and cohesion in the presence of graphene nanoparticles: Investigation of graphene nanosheets/ethylene glycol surface tension

Literature overview has affirmed that the presence of nanoparticles causes conflicting behaviors in surface tension, thereby, further studies are necessary to investigate the surface tension behavior. In this research, the base fluid surface tension behavior in the presence of graphene nanosheets is examined. The surface tension of the prepared samples at concentrations of 0–5 wt% was measured by SITA dynotester (SITA Process Solutions, Germany) at temperatures of 25–70°C. Based on the results, incorporation of graphene nanosheets into ethylene glycol weakens the cohesion between the ethylene glycol (EG) molecules. In other words, a part of the cohesive is replaced by the van der Waals force correspond to the nanoparticles presence as well as adhesive force between the EG and nanoparticle molecules. However, the effects of the increase in adhesive force were not able to counteract the cohesive force reduction efficacy, hence the presence of nanoparticles reduced the surface tension up to 13.9%. As the temperature raised from 25 to 70°C, the base fluid surface tension diminished by 8.3%, while for nanofluid at 5 wt%, this figure was 3.86%. Therefore, by using nanoparticles, the sensitivity of surface tension to temperature diminished.

Aggregation of Molecules in Liquid Ethylene Glycol and Its Manifestation in Experimental Raman Spectra and Non-Empirical Calculations

Intra- and intermolecular interactions in liquid ethylene glycol have been studied using the Raman spectroscopy method and non-empirical calculations. The results of non-empirical calculations show that an intermolecular hydrogen bond is formed between the hydrogen atom of the OH group in one ethylene glycol molecule and the oxygen atom in the other molecule. The formation of this bond gives rise to a substantial redistribution of charges between those atoms, which, nevertheless, insignificantly changes the bond length. In the corresponding Raman spectra, the presence of hydrogen bonds between the ethylene glycol molecules manifests itself as the band asymmetry and splitting.

Study on cytotoxicity of polyethylene glycol and albumin bovine serum molecule–modified quantum dots prepared by hydrothermal method

Abstract

Optimization of Click Chemistry for Bioconjugation

Application of the expanded genetic code has created specialized proteins that enable new methods to investigate biological systems. Biomaterials and antibody‐drug conjugations and often employ “click chemistry” utilizing copper(I)‐catalyzed azide‐alkyne cycloaddition. We have functionalized green fluorescent protein (GFP) by incorporating a non‐standard amino acid (nsAA), p‐Azido‐phenylalanine. However, the literature on the rate and yield of this reaction remains incomplete. To enhance bioconjugation, we have explored and optimized reaction conditions and stoichiometry. We employed two corroborating assays to test single‐ and double‐click reaction events: size exclusion chromatography and a fluorescence polarization assay. We evaluated the efficiency of a single click reaction between a small molecule fluorophore and our functionalized GFP. Completed click reactions were run through a purification column and fluorescence readings of eluted samples were used to evaluate yield. Analysis of this single click event was also conducted through a fluorescence polarization assay. This allows the determination of the reaction rate and yield in real time. Additionally, yield of double click reactions between two functionalized proteins and a polyethylene glycol (PEG) molecule with two alkyne handles has been evaluated using SDS‐PAGE. Through these efforts, we report reaction yields that surpass previously reported values. These advances support the improved employment of click chemistry for broad applications in biofunctionalization such as the development of biomaterials and antibody‐drug conjugatesSupport or Funding InformationFunding and support provided by the Cal Poly Chemistry and Biochemistry Department, the Center for Applications in Biotechnology, and the National Science Foundation.

PEG modification enhances the in vivo stability of bioactive proteins immobilized on magnetic nanoparticles.

To increase the in vivo stability of bioactive proteins via optimized loading methods. β-Glucosidase (β-Glu), as a model protein, was immobilized on magnetic nanoparticles(denoted as MNP-β-Glu) by chemical coupling methods and was further modified by poly(ethylene glycol) (PEG) molecules (denoted as MNP-β-Glu-PEG) to increase its stability. The physicochemical properties of the as-prepared nanohybrids, including the particle size, zeta potential, and enzyme activity, were well characterized. The proper MNP/β-Glu feed ratio was important for optimizing the particle size. Analysis of enzyme activity showed that the stability of immobilized β-Glu compared with free β-Glu was lower in deionized water and higher in blood serum at 37°C. MNP-β-Glu-PEG retained 77.9% of the initial activity within 30days at 4°C, whereas the free enzyme retained only 58.2%. Pharmacokinetic studies of Sprague-Dawley (SD) rats showed that the MNP-β-Glu-PEG group retained a higher enzyme activity in vivo (41.46% after 50min) than the MNP-β-Glu group (0.03% after 50min) and the β-Glu group (0.37% after 50min). Moreover, in contrast to the MNP-β-Glu group, the enzyme activity was not fully synchronous with the decrease in the Fe concentration in the MNP-β-Glu-PEG group. All findings indicated that the method of immobilization on magnetic nanoparticles and PEG modification is promising for the application of bioactive proteins in vivo.

A transistor-based label-free immunosensor for rapid detection of tau protein

Tau protein in cerebrospinal fluid (CSF) is a central and relevant biomarker of Alzheimer’s disease (AD) that correlates with the severity of dementia. Unfortunately, so far, direct label-free detection of tau remains a challenge. Here, we present a transistor-based biosensor that detects the net charge of tau protein directly under physiological conditions. To achieve this, readily available whole anti-tau IgG antibodies are co-immobilized on the sensor surface with polyethylene glycol (PEG) molecules of different molecular weight. We show that by increasing the PEG size from 10 kDa to 20 kDa, the electrical response upon binding of tau improves significantly. These results support recent theoretical work that predicted larger PEGs to form a thicker surface layer with a higher detectable analyte charge. With 20 kDa PEG, we demonstrate label-free tau detection in a wide concentration range with detection limits <1 pM in 150 mM buffer and cell culture media, as well as < 10 pM in artificial CSF. This purely electrical method allows fast and simple tau detection within 30 min without sample processing, washing steps, or labeled detection antibodies. By exchanging the capture antibody, the platform is also amenable to different biomarkers and may enable future diagnostic tools for AD and other diseases.

How Hydration Affects the Microscopic Structural Morphology in a Deep Eutectic Solvent.

Recently, it has been observed that choline chloride ([Ch][Cl]) based deep eutectic solvents (DESs) may possess nanostructures in which chloride ions play a major role by providing a backbone for the bridged hydrogen bond network. In this article, we present a fundamental study on the role of hydration on the nanostructure of a [Ch][Cl] based DES, ethaline. In this molecular dynamics investigation, we observe a nonlinear change in the structural morphology of ethaline on gradual addition of water. The initiation of disruption of the native structure of the DES at 40 mol % of water is clearly observed, after which the increasing dilution rapidly destructs the long-range as well as short-range intermolecular interactions existing between the constituent species of pure ethaline. Herein, we find that, at very high hydration level, chloride ion no longer acts as a bridge between the choline cation and ethylene glycol, as it forms strong hydrogen bond with water. Intriguingly, the strengthening of hydrogen bonding interactions among the ethylene glycol molecules is observed on increasing hydration level. Hence, it is predicted that segregation of ethylene glycol can occur in the pool of aqueous mixtures of [Ch][Cl] at very high hydration level.

Anticancer Therapeutics Decorated Nanomaterials

The cause of cancer diseases is dependent on various internal and external factors including inherited immune conditions, and genetic mutations and unhealthy diet, tobacco-chewing and smoking habits, and infections, respectively. Nanoscale drug delivery platforms have shown promising clinical results in several types of cancer and inflammatory disorders. Nanoparticles have special characteristics of high surface to volume ratio, size controllability, and can be easily functionalized during synthesis. Cytotoxic therapeutics adsorbed to nanoparticles are used during hormone therapy, immunotherapy, chemotherapy, etc. which preferentially kill the rapidly dividing cancer cells while minimizing the damage to the normal tissue. The toxic core of inorganic nanoparticles is protected by providing a physical barrier (functional polymers) between the core and the external environment. After linking to poly (ethylene glycol) molecules, the polymer-coated toxic dots did not change their optical and colloidal properties over a broad range of external environment conditions. This spontaneous encapsulation process removes the problems of particle aggregation in physiological buffers.

Luminescent Nanocomposites for Biomedical Applications

In this work, we pursue a concept of the multimodal drug preparation based on LuAG:Ce3+ nanoparticles. The functionality studied in this article is focused on the bioimaging of living cells via cathodoluminescence (CL) of scintillating nanoparticles attached to the cell surface. LuAG:Ce3+ scintillating nanoparticles were used as a core; amorphous or mesoporous SiO2 was used as a shell encapsulating the core to increase the surface reactivity; anti-Fas ligand (FasL) antibody was then attached to the outer shell in order to specifically bond the nanocomposite to the cell receptors; finally, polyethylene glycol molecules were attached to increase the biocompatibility of the nanocomposites. CL bioimaging was tested on yeasts Saccharomyces cerevisiae and leukocytes. It was found that the nanocomposites are able to attach to the cells via sorption or bonding to the receptors. The prepared nanocomposite shows stable luminescence under 10-keV electron irradiation, thus making a prospective candidate for this application and future multimodal drug design.

Recent Developments in the Design of Non-Biofouling Coatings for Nanoparticles and Surfaces.

Biofouling is a major issue in the field of nanomedicine and consists of the spontaneous and unwanted adsorption of biomolecules on engineered surfaces. In a biological context and referring to nanoparticles (NPs) acting as nanomedicines, the adsorption of biomolecules found in blood (mostly proteins) is known as protein corona. On the one hand, the protein corona, as it covers the NPs’ surface, can be considered the biological identity of engineered NPs, because the corona is what cells will “see” instead of the underlying NPs. As such, the protein corona will influence the fate, integrity, and performance of NPs in vivo. On the other hand, the physicochemical properties of the engineered NPs, such as their size, shape, charge, or hydrophobicity, will influence the identity of the proteins attracted to their surface. In this context, the design of coatings for NPs and surfaces that avoid biofouling is an active field of research. The gold standard in the field is the use of polyethylene glycol (PEG) molecules, although zwitterions have also proved to be efficient in preventing protein adhesion and fluorinated molecules are emerging as coatings with interesting properties. Hence, in this review, we will focus on recent examples of anti-biofouling coatings in three main areas, that is, PEGylated, zwitterionic, and fluorinated coatings.

Selective Phase Control of Dopant-Free Potassium Sodium Niobate Perovskites in Solution.

As one of the perovskite families, potassium sodium niobates (K1-xNax)NbO3 (KNN) have been gaining tremendous attention due to their various functional properties which can be largely determined by their crystallographic phase and composition. However, a selective evolution of different phases for KNN with controlled composition can be difficult to achieve, especially in solution chemical synthesis because of its strong tendency to stabilize into orthorhombic phase at conventional synthetic temperature. We herein developed a facile solution approach to control the phase and composition of dopant-free KNN particles selectively through the modification of reaction parameters. A conventional hydrothermal synthesis method yielded orthorhombic KNN particles, while the monoclinic phase, which has never been observed in a bulk counterpart, was kinetically generated by the compositional modification of an intermediate phase under a high-intensity ultrasound irradiation. Cubic KNN particles were stabilized when ethylene glycol was used as a co-solvent together with deionized water through bonding between ethylene glycol molecules and the surface of the KNN. Composite-structured piezoelectric harvesters were fabricated using each phase of KNN particles and the β-phase poly(vinylidene fluoride-co-trifluoroethylene) polymer. Maximum output power was found for the harvester containing orthorhombic KNN particles. This facile synthetic methodology could pave a new pathway for fabricating numerous phase-controlled materials.

Density, viscosity, and spectroscopic and computational analyses for hydrogen bonding interaction of 1,2-propylenediamine and ethylene glycol mixtures

Density and viscosity of 1, 2-propylenediamine (PDA) and ethylene glycol (EG) mixtures with various ratios in the temperature range of 298.15 to 318.15 K with the step of 5 K under atmospheric pressure were measured. In accordance with it, the excess properties and thermodynamic quantities of the solutions were calculated. In addition, by means of spectroscopic analyses and computational chemistry, the hydrogen bonding interaction between the nitrogen atom in the PDA molecules and the alcoholic hydroxyl group in the EG molecules was demonstrated, which can be used to explain the changes in physicochemical properties of mixed solution. The results are interpreted as the form of CH2(OH)CH2OH⋯NH2CH2CH(NH2)CH3 in accordance with a cross-linking and hydrogen bonding interaction between the amine molecules and the alcohol molecules.

In Russian

Hydrophobic spin-labeled carboline and a number of spin-labeled steroids dissolve well in both pure PEG and aqueous PEG solutions, demonstrating the presence of a triplet in the EPR spectrum. It was shown that the introduction of 20% aqueous solutions of PEG mol. m. from PEG-200 to PEG-40,000, the hydrophobic spin of labeled progesterone or carboline from the hydrophobic cavity of SAB is effectively displaced into the solution of bovine serum albumin (SAB) by competing with the hydrophobic cavity of SAB. Polyethylene glycols demonstrate full biocompatibility even with hydrophobic biological structures and, as biocompatibility enhancers, are universal. Analysis of the curve of the dependence of PEG microviscosity on mol. m. shows the presence of an inflection point on the curve in the area of the pier. m. 300-400, which indicates the compaction of the structure of PEG and corresponds to published data on the partial helixing of a polyethylene glycol molecule, starting with PEG-400 and above, in which the main role is played by hydrogen bonds of the PEG molecule. Methylene hydrophobic PEG residues appear inside the polyethylene glycol helix, and the polar groups providing the PEG molecules with osmotically active properties and causing dehydration of cell membranes appear outside the PEG helix. Therefore, with the growth of mol. m. PEG ability to dehydrate cells increases. Apparently, the mechanism of increasing PEG biocompatibility is the ability of PEG molecules to compact, spiralize, or expand molecules to accept the optimal conformation of the structure, providing their hydrophobic or polar groups for optimal binding on the one hand to nanoparticles and, on the other, to a bioobject. The introduction of conjugates of PEG nanoparticles into cells, which oppositely affects the microviscosity of membranes and compensates for the negative effect of nanoparticles on membranes, is the second mechanism for increasing the biocompatibility of nanoparticles. The possibility of the interaction of PEG with nanochorns with the orientation of PEG units along the cone needles (nanotubes) of nanochorns has been shown to increase the biocompatibility of nanochorns.

Low temperature light-assisted hydrogen production from aqueous reforming ethylene glycol over Pt/Al2O3 and Pd/Al2O3 catalysts

Al2O3 supported Pt and Pd nanoparticle catalysts were prepared by impregnation-reduction method, and employed in the photocatalytic aqueous-phase reforming of ethylene glycol. Light illumination can decrease the reaction activation energy remarkably. Pt/Al2O3 exhibits much higher H2 turnover frequency (TOF) and lower CO selectivity than Pd/Al2O3 catalyst. Their morphology and structure were characterized by XRD, TEM, UV-vis techniques. In situ diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) indicates light can promote the cleavage of O–H bonds of ethylene glycol molecule. DFT calculation suggests the lower CO selectivity over Pt/Al2O3 catalyst can be attributed to the low energy barriers of reaction in the step of CO+O→CO2.

Tailoring Kidney Transport of Organic Dyes with Low-Molecular-Weight PEGylation.

Subtle changes in size can induce distinct responses of the body to hard nanomaterials; however, it is largely unknown whether just a few ethylene oxide unit differences in soft poly(ethylene glycol) (PEG) molecules could significantly alter the renal clearance of small molecules. By systematically investigating in vivo transport of the representative renal clearable organic dyes, IRDye800CW after being conjugated with a series of PEG molecules with molecular weight (MW) below 10 kDa, we found a MW-dependent scaling law: PEG45 (MW = 2100 Da) is an optimized MW to generate the most efficient renal clearance for IRDye800CW by expediting the glomerular filtration of organic dyes and reducing their nonspecific interactions with background tissue. Moreover, the uniqueness of PEG45 can be generalized to other organic dyes such as ZW800-1 and fluorescein. This finding highlights the importance of low-MW PEGylation in tailoring in vivo transport of organic fluorophores, which would broaden their biomedical applications.