Polyethylene Glycol Aldehyde Research Articles

Quaternary ammonium carboxymethyl chitosan composite hydrogel with efficient antibacterial and antioxidant properties for promoting wound healing

Multifunctional hydrogels have been developed to meet the various requirements of wound healing. Herein, an innovative hydrogel (QCMC-HA-PEG) was formed through the Schiff base reaction, composed of quaternary ammonium-modified carboxymethyl chitosan (QCMC), hyaluronic acid (HA), and 8-arms Polyethylene Glycol aldehyde (8-ARM-PEG-CHO). The resulting hydrogels exhibited good mechanical and adhesive properties with improved antibacterial efficacy against both Gram-positive and Gram-negative bacteria compared to CMC hydrogels. QCMC-HA-PEG hydrogels demonstrated remarkable adhesive ability in lap-shear test. Furthermore, the incorporation of MnO2 nanosheets into the hydrogel significantly enhanced its reactive oxygen species (ROS) scavenging and oxygen generation capabilities. Finally, experimental results from a full-thickness skin wound model revealed that the QCMC-HA-PEG@MnO2 hydrogel promoted skin epithelization, collagen deposition, and inflammatory regulation significantly accelerated the wound healing process. Therefore, QCMC-HA-PEG@MnO2 hydrogel could be a promising wound dressing to promote wound healing.

Preparation of dehydroabietyl polyethylene glycol aldehyde modified hydroxyethyl chitosans and their physicochemical properties

A series of polymeric surfactants based on monodehydroabietyl polyoxyethylene(5) ether (DHA(EO)5H) and hydroxyethyl chitosan (HEC) were prepared through a three-step process. First, DHA(EO)5H was oxidized using activated MnO2 and transformed into dehydroabietyl polyethylene glycol(5) aldehyde (DHA(EO)4CH2CHO). Then, the DHA(EO)4CH2CHO was reacted with HEC and converted into Schiff-base. Finally, the polymeric surfactant, DHA(EO)4CH2CHO modified HEC (DHA(EO)4CH2CHO-m-HEC), was obtained by reducing the Schiff-base with sodium borohydride. The grafting degree (DG) of DHA(EO)4CH2CHO substitution onto HEC for DHA(EO)4CH2CHO-m-HECs was determined using elemental analysis (EA), and the surface activities and foam performance of DHA(EO)4CH2CHO-m-HECs in aqueous solution were investigated respectively. The emulsifying capacities of DHA(EO)4CH2CHO-m-HECs were evaluated according to the stability times of emulsion composed of water and liquid paraffin. The experimental results showed the DG could have significant influence on the critical micelle concentration (cmc) of DHA(EO)4CH2CHO-m-HECs and their surface tensions at cmc (γcmc), but nearly no effect on their minimum surface tensions (γmin) in aqueous solution. Among the synthetic polymeric surfactants in this investigation, DHA(EO)4CH2CHO-m-HEC with DG of 56.95% exhibited the best emulsification and foam properties.

A PEG-CMC-THB-PRTM hydrogel with antibacterial and hemostatic properties for promoting wound healing

The introduction of antibacterial and hemostatic hydrogels with good mechanical properties that display desirable impacts on wound healing process is still an unmet essential for clinical wound dressings. Herein, a multifunctional hydrogel PEG-CMC-THB-PRTM was fabricated via a one-pot method combining carboxymethyl chitosan (CMC), 2,3,4-trihydroxybenzaldehyde (THB), protamine (PRTM) and 4-arm polyethylene glycol aldehyde (PEG). The hydrogel was formed by the dynamic Schiff base reaction between amino groups of carboxymethyl chitosan and aldehyde groups of 4-arm polyethylene glycol aldehyde and exhibited excellent mechanical properties. The developed hydrogel also showed outstanding effects on anti-bacteria and hemostasis through the release of PRTM. Moreover, the hydrogel could promote extracellular matrix formation and wound closure in vivo, thereby accelerating the healing of skin wound. These results suggested that the multifunctional PEG-CMC-THB-PRTM hydrogel is a promising candidate for the clinical treatment of full-thickness wounds.

Engineering of surface modified Ti3C2Tx MXene based dually controlled drug release system for synergistic multitherapies of cancer

Easily surface-modified MXenes have been extensively investigated as nanoplatforms for drug delivery because of their high drug-loading capacity, multiple drug release modes, and good biocompatibility. Herein, we report the synthesis of an MXene@Au-PEG drug delivery platform for the high loading of the chemotherapeutic doxorubicin (DOX), which has both near infrared (NIR) laser-triggered and pH-responsive drug release modes. Owing to surface modification with thiol polyethylene glycol aldehyde chains (SH-PEG-CHO) connected to the MXene by Au nanoparticles (Au NPs), the MXene@Au-PEG-DOX system shows good photothermal stability, biosafety, and histocompatibility during in vivo and vitro tests. Additionally, based on the good photothermal conversion capability of both Au particles and MXene, the system exhibits synergistic photothermal ablation and chemotherapy for tumor treatment. The passively targeted release properties of the MXene@Au-PEG drug delivery platform also enhance the cellular uptake of DOX at tumor sites, thereby improving the efficiency of the drug. Thus, the reported preparation strategy for a surface-modified MXene-based drug delivery platform with high drug-loading capacity, multiple drug release modes, and synergistic therapy, provides a promising demonstration of the potential application of MXene-based nanomaterials for cancer treatment.

Structural and biochemical evidence that ATP inhibits the cancer biomarker human aldehyde dehydrogenase 1A3

Human aldehyde dehydrogenase (ALDH) participates in the oxidative stress response and retinoid metabolism, being involved in several diseases, including cancer, diabetes and obesity. The ALDH1A3 isoform has recently elicited wide interest because of its potential use as a cancer stem cell biomarker and drug target. We report high-resolution three-dimensional ALDH1A3 structures for the apo-enzyme, the NAD+ complex and a binary complex with ATP. Each subunit of the ALDH1A3-ATP complex contains one ATP molecule bound to the adenosine-binding pocket of the cofactor-binding site. The ATP complex also shows a molecule, putatively identified as a polyethylene glycol aldehyde, covalently bound to the active-site cysteine. This mimics the thioacyl-enzyme catalytic intermediate, which is trapped in a dead enzyme lacking an active cofactor. At physiological concentrations, ATP inhibits the dehydrogenase activity of ALDH1A3 and other isoforms, with a Ki value of 0.48 mM for ALDH1A3, showing a mixed inhibition type against NAD+. ATP also inhibits esterase activity in a concentration-dependent manner. The current ALDH1A3 structures at higher resolution will facilitate the rational design of potent and selective inhibitors. ATP binding to ALDH1A3 enables activity modulation by the energy status of the cell and metabolic reprogramming, which may be relevant in several disease conditions.

PEG-DOX, novel pH responsive prodrug nanoparticles

pH responsive prodrug nanoparticles (PEG-DOX) were prepared by attaching free Doxorubicin ( DOX) onto the amphipathic polyethylene glycol-aldehyde (PEG-CHO). The hydrophobic core of PEG-CHO enabled free DOX to be attached, while the hydrophilic outer layer of the carrier enabled the water solubility of the entire structure. This nanocarrier enabled a greater carrying capacity than free DOX, making its circulation time longer. The prodrug remained stable within neutral pH, ensuring its prolonged circulation time, but disassembled rapidly when reaching in the acidic environment of tumor tissues to release the free DOX. The newly designed nanocarriers have the potential to be applied clinically as a future DOX formulation in cancer chemotherapy.

Biophysical and biological characterization of PEGylated recombinant human endostatin.

Recombinant human endostatin (MES), showing potent inhibition on angiogenesis and tumour growth, has great potential as a therapeutic agent for tumours. The aim of this study was to evaluate the biophysical and biological characterization of PEGylated recombinant human endostatin (M2 ES). Recombinant human endostatin was mono-PEGylated by conjugation with methoxy polyethylene glycol aldehyde (mPEG-ALD), and the modification site was identified by digested peptide mapping and matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). The purity was assessed by SDS-PAGE, high-performance liquid chromatography (HPLC), and capillary zone electrophoresis. The physicochemical property was analyzed through fluorescence spectroscopy, and circular dichroism. The bioactivity and anti-tumour efficacy of M2 ES were evaluated using an in vitro endothelial cell migration model and a null-mouse xenograft model of a prostatic cancer, respectively. M2 ES molecules contain a single 20kDa mPEG-ALD molecule conjugated at the N-terminal portion of MES. The purity of M2 ES was greater than 98%. The physicochemical analysis demonstrated that PEGylation does not change the secondary and tertiary structure of MES. Notably, M2 ES retards endothelial cell migration and tumour growth when compared to control group. These biophysical and biological characterization study data contribute to the initiation of the ongoing clinical study.

Synthesis and characterisation of iron oxide nanoparticles conjugated with epidermal growth factor receptor (EGFR) monoclonal antibody as MRI contrast agent for cancer detection.

The aim of this study is to synthesise superparamagnetic iron oxide nanoparticles conjugated with anti-epidermal growth factor receptor monoclonal antibody (ANTI-EGFR-SPION) and investigate its physicochemical characterisation and biocompatibility as a targeted magnetic resonance imaging (MRI) contrast agent for the EGFR-specific detection in EGFR expressing tumour cells. These particles employed biocompatible polymers, poly(D,L-lactide-co-glycolide) (PLGA) and polyethylene glycol aldehyde (PEG-aldehyde), to increase the half-life of particles in circulation and reduce their side effects. The Fe3O4-loaded PLGA-PEG-aldehyde nanoparticles were prepared by a modified water-in-oil-in-water double emulsion method. The EGFR antibody was conjugated to the surface of SPIONs using the aldehyde-amine reaction. Synthesised conjugates (nanoprobes) were characterised using Fourier transform infrared spectrophotometry, dynamic light scattering, transmission electron microscopy images, and vibrating-sample magnetometery, and the results showed that the conjugation was successful. The mean diameter of nanoprobes was about 25 nm. These nanoprobes exhibited excellent water-solubility, stability, and biocompatibility. Meanwhile, MR susceptibility test proved that synthesised nanoprobes can be managed for negative contrast enhancement. The results of this study suggested the potential use of these nanoprobes for non-invasive molecular MRI in EGFR detection in the future.

Synthesis of Polyethylene Glycol Aldehyde Derivatives by Ozonation

Synthesis of Polyethylene Glycol Aldehyde Derivatives by Ozonation

Synthesis of Zn-Doped Manganese Ferrite Nanoparticles Via Coprecipitation Method for Magnetic Resonance Imaging Contrast Agent

Two different preparations of biocompatible magnetic nanoparticles (MNPs), both (MnFe2O4 and Mn0.91Zn0.09Fe2O4) coated with methoxy polyethylene glycol aldehyde (m-PEG-CHO) were prepared through coprecipitation method. The prepared powder was reanalyzed for material structure with an X-ray diffractometer (XRD) and for particle size using a transition electron microscope (TEM). Magnetic saturation (MS) and coercivity (HC) of the formed particles were examined by a vibrating sample magnetometer (VSM). Surface structure of the samples was characterized by Fourier transform infrared spectroscopy (FTIR). Biocompatible ferrofluids were intravenously injected into four rabbits. Then the magnetic resonance (MR) images of brain were obtained by magnetic resonance imaging (MRI) experiments before and after intravenous injection of ferrofluids. The MNPs demonstrate super paramagnetic behavior with a spinel structure measuring 30–40 nm in size. Doping of these magnetite nanoparticles with zinc resulted in decreases in crystallite size from 24.23 nm to 21.15 nm, the lattice parameter from 8.45 Å to 8.43 Å and the coercivity from 41.20 Oe to 13.07 Oe. On the other hand, saturation magnetization increased from 50.12 emu/g to 57.36 emu/g following zinc doping. Image exposure analysis revealed that the reduction of MR signal intensity for zinc-doped magnetite nanoparticles was more than nondoped nanoparticles (shorter T2 relaxation time) thereby making the images darker.

Preparation, characterization and in vitro bioactivity of N-terminally PEGylated staphylokinase dimers

PEGylation can improve the therapeutic efficacy of proteins by increasing serum half-life of proteins and reducing immunogenicity and antigenicity. However, PEGylation results in a substantial loss of the bioactivity of proteins due to the steric hindrance of polyethylene glycol (PEG). Dimerization of the proteins is an efficient approach to increase the bioactivity of the PEG–protein conjugates. Here, staphylokinase (SAK) was used due to its therapeutic potential for coronary thrombolysis. SAK dimers (dSAK) were prepared by engineering cysteine residue at the C-terminus of SAK and dimerization of the cysteine residue with 1,4-bismaleimidobutane. PEG aldehyde was used for site-specific PEGylation of dSAK at one of its two N-termini. Structural analysis indicated that dimerization of SAK can decrease the steric hindrance of PEG and increase the binding affinity of PEG–SAK to plasminogen. Dimerization of SAK increased the relative bioactivity of PEG–SAK from 39.0% to 62.0%. Therefore, site-specifically PEGylated dSAK at one of its two N-termini has higher bioactivity than the N-terminal PEGylated SAK.

N-terminal specificity of PEGylation of human bone morphogenetic protein-2 at acidic pH

Site-specific PEGylation offers the possibility to modify a therapeutic protein without interfering with its biological activity. Previously, a preferential N-terminal PEGylation has been reported for several proteins when the reaction was performed at acidic pH. In the present study it was explored if acidic pH favors N-terminal PEGylation of bone morphogenetic protein-2 (BMP-2). PEGylation by poly(ethylene glycol) aldehyde (PEG-AL) or poly(ethylene glycol) carboxymethyl succinimidyl ester (PEG-NHS) was performed at moderate acidic pH of 4. Comparing with PEG-NHS, PEG-AL converted more BMP-2 mainly to mono- or di-PEGylated derivatives at much less molar excess and shorter duration. Analysis of Tryptic fragments of the PEGylated derivatives indicated a partial N-terminal PEGylation specificity. PEG-AL exhibited higher specificity than PEG-NHS. UV spectrometry proved that PEGylation improved the solubility of BMP-2 in PBS. Surface plasmon resonance showed that PEGylation decreased the binding of BMP-2 proteins to a type II receptor. Remarkably, mono-PEGylated BMP-2 with PEG-AL showed higher cellular bioactivity than unmodified protein. Higher N-terminal PEGylation specificity correlates with higher receptor binding affinity and cellular activity. In summary, PEGylation of BMP-2 by PEG-AL and PEG-NHS at acidic pH exhibits a partial N-terminal specificity which however might be sufficient for an efficient site-specific PEGylation process.

A new ether bond-splitting enzyme found in Gram-positive polyethylene glycol 6000-utilizing bacterium, Pseudonocardia sp. strain K1

Pseudonocardia sp. strain K1 is the only Gram-positive bacterium among the bacteria aerobically metabolizing polyethylene glycol (PEG). Generally, PEG is metabolized by an oxidative pathway in which a terminal alcohol group of PEG is oxidized to aldehyde and to carboxylic acid and then an ether bond is oxidatively cleaved. As the cell-free extract of Pseudonocardia sp. strain K1 has PEG dehydrogenase, PEG aldehyde dehydrogenase and diglycolic acid (DGA) dehydrogenase (DGADH) activities, all of which are constitutively formed, the strain has a metabolic pathway similar to that so far known. We purified an ether bond-splitting enzyme as DGADH. The molecular mass of the enzyme was estimated to be 55 kDa; and it consisted of two identical subunits. The enzyme oxidatively cleaved both an ether bond of PEG 3000 dicarboxylic acid and DGA. The N-terminal amino acid sequence of the purified enzyme had high homology with various superoxide dismutases and the enzyme had also superoxide dismutase activity. The atomic absorption spectrum showed that approximately one atom of Fe was included in each subunit of the enzyme. DGADH activity increased in the cells grown in a PEG medium supplemented with FeCl(3). Thus, we concluded that the enzyme purified from Pseudonocardia sp. strain K1 is a new ether bond-splitting enzyme.