Aminated Polyethylene Glycol Research Articles

A cellulose nanocrystal-carbon dots@cholestrol fluorescent probe for imaging of plasma membrane with extended time scale

Despite the advancement of plasma membrane imaging techniques, there is an unmet need for fluorescent probes which can “light up” the lipid bilayer with an extended time scale. In this work, a novel fluorescent probe is developed for imaging of plasma membrane. The probe comprises a cellulose nanocrystal (CNC) scaffold derived from low-cost wood pulp, carbon dots (CDs) fluorophore that is in-situ synthesized on the surface of CNC, and cholesterol (Chol) ligand with aminated polyethylene glycol (PEG) spacer. In the CNC-CDs@PEG-Chol configuration, the Chol ligand provides excellent binding affinity onto plasma membrane due to its hydrophobic nature, while CDs contribute to the marvelous optical stability, as well as the high quantum yield of the fluorescent probe. For CNC scaffold, their unique morphological property allows the assembling of dense Chol ligands, and more importantly, impedes the diffusions of imaging moieties into the cytoplasm. Therefore, the fluorescent probe is featured with remarkable specificity and satisfying plasma membrane imaging time window, which covers the co-incubation time from 30 to 90 min. In contrast, the mono-dispersed CDs@PEG-Chol probe can be facilely internalized by the cells at a co-incubation time as short as 20 min. CNC is proven to be responsible for the different imaging time scales by providing the confinement effects. The proposed fluorescent probe is believed to be a promising tool for studying the plasma membrane behaviors associated with cellular physiological processes.

Biotin-Conjugated Upconversion KMnF3/Yb/Er Nanoparticles for Metabolic Magnetic Resonance Imaging of the Invasive Margin of Glioblastoma

The incomplete detection of glioblastoma or the remnants of surgery constitute the primary reasons underlying glioblastoma recurrence. However, the current commercial MR Gd-based contrast agents (GBCAs) are not specialized, thus posing a potentially high risk of missed diagnosis or inaccurate boundary identification. MR contrast agents have been widely explored in conjugation with tumor-specific markers to preoperatively diagnose and identify the intraoperative positioning of glioblastoma. Herein, we developed a type of upconversion nanoparticle (UCNP), KMnF3:18%Yb, 2%Er, via the typical hydrothermal method, which possesses unique MR upconversion luminescence bimodal imaging. Furthermore, UCNPs were transformed to the aqueous phase by replacing oleic acid with amine–polyethylene glycol (PEG)–thiol (NH2–PEG–SH), further enabling the covalent conjugation of the glioblastoma metabolic ligand biotin. The as-prepared multifunctional biotin/PEG–UCNPs were characterized using various techniques. Moreover, their biocompatibility, especially with the brain, was systematically assessed via histological and hematological examinations. The results indicated negligible toxicity in vivo. As a proof of concept, biotin/PEG–UCNPs exhibited considerable potential for accurate definition of glioma infiltration boundaries for surgery as metabolic dual imaging contrast agents.

A snowboard-inspired lubricating nanosystem with responsive drug release for osteoarthritis therapy

Most of present works of osteoarthritis (OA) therapy are focusing on reducing friction and improving drug loading capacity, while little attention is paid to realizing long-time lubrication and on-demand drug release. In this study, inspired by snowboards with good solid–liquid interface lubrication, a fluorinated graphene based nanosystem with dual functions of long-time lubrication and thermal-responsive drug release was constructed for OA synergetic therapy. An aminated polyethylene glycol bridging strategy was developed to enable covalent grafting of hyaluronic acid on fluorinated graphene. This design not only greatly increased the nanosystem’s biocompatibility, but also reduced the coefficient of friction (COF) by 83.3 % compared to H2O. The nanosystem showed long-time and steady aqueous lubrication behavior even after more than 24,000 times of friction tests, and a low COF of 0.13 was obtained with over 90% wear volume reduction. Diclofenac sodium was controllably loaded and sustained drug release was tuned by near-infrared light. Moreover, anti-inflammation results showed that the nanosystem had good protective effect on inhibiting OA deterioration, which could up-regulate cartilage anabolic genes of Col2α and aggrecan while down-regulating catabolic proteases genes of TAC1 and MMP1. This work constructs a novel dual-functional nanosystem that realizes friction and wear reduction with long lubrication life, and shows thermal-responsive on-demand drug release with good synergistic therapeutic effect of OA.

Direct Electrochemistry of Glucose Dehydrogenase-Functionalized Polymers on a Modified Glassy Carbon Electrode and Its Molecular Recognition of Glucose.

A glucose biosensor was layer-by-layer assembled on a modified glassy carbon electrode (GCE) from a nanocomposite of NAD(P)+-dependent glucose dehydrogenase, aminated polyethylene glycol (mPEG), carboxylic acid-functionalized multi-wall carbon nanotubes (fMWCNTs), and ionic liquid (IL) composite functional polymers. The electrochemical electrode was denoted as NF/IL/GDH/mPEG-fMWCNTs/GCE. The composite polymer membranes were characterized by cyclic voltammetry, ultraviolet-visible spectrophotometry, electrochemical impedance spectroscopy, scanning electron microscopy, and transmission electron microscopy. The cyclic voltammogram of the modified electrode had a pair of well-defined quasi-reversible redox peaks with a formal potential of -61 mV (vs. Ag/AgCl) at a scan rate of 0.05 V s-1. The heterogeneous electron transfer constant (ks) of GDH on the composite functional polymer-modified GCE was 6.5 s-1. The biosensor could sensitively recognize and detect glucose linearly from 0.8 to 100 µM with a detection limit down to 0.46 μM (S/N = 3) and a sensitivity of 29.1 nA μM-1. The apparent Michaelis-Menten constant (Kmapp) of the modified electrode was 0.21 mM. The constructed electrochemical sensor was compared with the high-performance liquid chromatography method for the determination of glucose in commercially available glucose injections. The results demonstrated that the sensor was highly accurate and could be used for the rapid and quantitative determination of glucose concentration.

Z-Scheme heterostructures for glucose oxidase-sensitized radiocatalysis and starvation therapy of tumors.

Although many semiconductor heterojunctions have been prepared to promote radiation-generated exciton separation for radiocatalysis therapy (RCT), most of them inevitably sacrifice the redox ability of radiation-generated electrons and holes. Herein, we design and construct BiOI/Bi2S3@polydopamine nanosheets modified by amine-polyethylene glycol-folic acid and glucose oxidase for glucose oxidase-sensitized RCT and starvation therapy (ST) synergistic therapy of tumors. The unique Z-scheme energy level arrangement between BiOI and Bi2S3 can elevate the charge separation efficiency, as well as maximize the redox ability of radiation-generated electrons and holes, leading to the enhancement of the therapeutic efficacy of RCT. Since glucose oxidase can supply excess H2O2 for RCT to produce ˙OH on one hand, but efficiently cut off the energy supply of tumor cells via ST, on the other hand, our nanosheets exhibit superior tumor therapeutic efficacy to any single treatment benefiting from the cascade and synergy effects between RCT and ST.

Synthesis and in Vitro anticancer properties of Cu2–xSe–AIPH nanomaterials

The Cu2–xSe nanoparticles were synthesized by high temperature pyrolysis, modified with aminated polyethylene glycol in aqueous solution and loaded with compound 2,2′–azobis[2–(2–imidazolin–2–yl)propane] dihydrochloride (AIPH). The obtained nanomaterials can induce photothermal effect and use heat to promote the generation of toxic AIPH radicals under the irradiation of near-infrared laser (808 nm), which can effectively kill cancer cells. A series of in vitro experiments can preliminarily prove that Cu2–xSe–AIPH nanomaterials have strong photothermal conversion ability, good biocompatibility and anticancer properties.

Exfoliated FePS3 nanosheets for T1-weighted magnetic resonance imaging-guided near-infrared photothermal therapy in vivo

Developing bifunctional nanoplatforms integrating advanced biological imaging with high-performance therapeutic functions is interesting for nanoscience and biomedicine. Herein, thin-layered FePS3 nanosheets modified with amine polyethylene glycol (FePS3-PEG) are synthesized by ultrasonicated exfoliation of bulk FePS3 single crystals under Ar atmosphere and in situ chemical functionalization with amine PEG. The prepared FePS3-PEG nanosheets give a photothermal conversion efficiency of 22.1% under 808-nm laser and evident T1 relaxation (r1 = 2.69 (mmol L−1)−1 S−1) in external magnetic fields. Biologically experimental results in vitro and in vivo demonstrate that FePS3-PEG nanosheets have good biocompatibility and exhibit excellent photothermal therapy (PTT) effect under clear T1 weighted magnetic resonance imaging (MRI). The characteristics of FePS3-PEG nanosheets enable them to be a promising nanomedicine for T1-weighted MRI-guided near-infrared PTT of cancers.

Molecular Dynamics Simulations of DNA Adsorption on Graphene Oxide and Reduced Graphene Oxide-PEG-NH2 in the Presence of Mg2+ and Cl− ions

Graphene and its functionalised derivatives are transforming the development of biosensors that are capable of detecting nucleic acid hybridization. Using a Molecular Dynamics (MD) approach, we explored single-stranded or double-stranded deoxyribose nucleic acid (ssDNA or dsDNA) adsorption on two graphenic species: graphene oxide (GO) and reduced graphene oxide functionalized with aminated polyethylene glycol (rGO-PEG-NH2). Innovatively, we included chloride (Cl−) and magnesium (Mg2+) ions that influenced both the ssDNA and dsDNA adsorption on GO and rGO-PEG-NH2 surfaces. Unlike Cl−, divalent Mg2+ ions formed bridges between the GO surface and DNA molecules, promoting adsorption through electrostatic interactions. For rGO-PEG-NH2, the Mg2+ ions were repulsed from the graphenic surface. The subsequent ssDNA adsorption, mainly influenced by electrostatic forces and hydrogen bonds, could be supported by π–π stacking interactions that were absent in the case of dsDNA. We provide a novel insight for guiding biosensor development.

Reductive response and RGD targeting nano-graphene oxide drug delivery system

Cancer cell therapy using redox response and targeted drug delivery systems can increase therapeutic effects of anti-cancer therapy. Here, we report a redox-responsive drug carrier based on nanoscale Graphene Oxide (GO) loaded with Doxorubicin (DOX). In this drug carrier demonstration, we utilized Arginine-glycine-aspartic acid (RGD) peptide, aminated polyethylene glycol (6ARM-PEG-NH2, PEG-NH2) to functionalize the GO. To integrate the carrier with a redox responsive property, we utilized disulfide linkages (3,3′-dithiodipropionic acid (DTPA)), which can be cleaved by glutathione (GSH) combined with the PEG-NH2. Our results show that DOX is rapidly released in a pH = 5.50 PBS solution with GSH concentration of 10 mM. The drug-loading system (RGD-GO-PEG-S-S-DOX) combined with photo-thermotherapy possesses good inhibition activity of Hep-G2 cells at a relatively low concentration. When the concentration of RGD-GO-PEG-S-S-DOX was 1.56 μg/mL, the inhibition activity of Hep-G2 cells was 78%. Because tumor cells generally exhibit a higher concentration of GSH than normal ones, and tumor blood vessels are distorted and dilated, and the blood flow resistance tends to be large, tumor cells are more sensitive to temperature changes than normal tissues. Thus, drug delivery systems, like the one we studied, have potential applications in a therapeutic strategy for the treatment of liver cancer.

Magnetic/pH dual‐responsive nanocomposites loading doxorubicin hydrochloride for cancer therapy

Development of stimuli-responsive nanocomposites for the delivery anticancer drug has attracted considerable attention. A magnetic/pH dual-responsive nanocomposite was synthesised by amide condensation reaction and developed for cancer therapy. The PEGylated citric-coated Fe 3 O 4 (PCI)-graphene oxide (GO) nanocomposites was constructed by a three-step process. Fe 3 O 4 magnetic nanoparticles were firstly coated with citric acid, and then covalently linked to aminated polyethylene glycol (NH 2 -PEG-NH 2 ); lastly, the PCI was covalently conjugated to graphite oxide to obtain PCI-GO nanocomposites. The PCI-GO nanocomposites were characterised by X-ray diffraction, scanning electron microscopy, Fourier transform-infrared, ultraviolet-visible, and thermogravimetry. The magnetic of nanocomposites was confirmed by a vibrating sample magnetometer. Due to the hydrogen bond, π - π stacking and electrostatic interaction between the doxorubicin (DOX) hydrochloride and PCI-GO nanocomposites, the PCI-GO nanocomposites could load DOX effectively and with a high drug loading content (about 87.6%). The DOX-loaded PCI-GO (DOX/PCI-GO) nanocomposites exhibited pH-responsive release behaviour. The DOX/PCI-GO nanocomposites could effectively inhibit tumour growth in vitro, which was comparable to the antitumour effect of free DOX. The result indicates that the PCI-GO nanocomposites exhibit great potential for a magnetic targeted drug delivery system in multimodal and synergistic cancer therapy.

Improved mechanical and dielectric performances of epoxy nanocomposites filled with aminated polyethylene glycol grafted graphene

Aminated polyethylene glycol (PEG-NH2) functionalized graphene nanosheets (PEG-rG) were successfully introduced into epoxy resin as a core-shell nanostructure to prepare the epoxy based dielectric composite. The overall mechanical and dielectric performances of the PEG-rG/epoxy nanocomposites were greatly improved in comparison with its counterparts employing with untreated graphene. The dielectric constant of PEG-rG/epoxy 1.5 wt% nanocomposites reached 84.3 at 100 Hz, two times higher than that of rG/epoxy 1.5 wt% system. What’s more, the dielectric loss is effectively reduced to a very low level (tan δ = 0.21).

Effect of polyethylene glycol surface charge functionalization of SWCNT on the in vitro and in vivo nanotoxicity and biodistribution monitored noninvasively using MRI

The current study evaluated in vitro and in vivo toxicity of carboxyl or amine polyethylene glycol (PEG) surface functionalization of single-walled carbon nanotubes (SWCNTs). Assessments of cytotoxicity, genotoxicity, immunotoxicity, and oxidative stress were performed in vitro and in vivo (in a 1-month follow-up study). The SWCNT biodistribution was investigated using noninvasive magnetic resonance imaging (MRI). Results confirmed the enhanced biocompatibility of PEG-functionalized SWCNTs compared to non-functionalized materials with significant decreases (p < 0.05) in the percentage of cell viability and increases in ROS generation, mitochondrial membrane potential, cell apoptosis, oxidative stress generation, and oxidative DNA damage in vitro. PEG-functionalized SWCNTs with amine terminals were found to induce prominent increases in ROS generation, mitochondrial membrane potential, and oxidative stress compared to carboxy functionalization. No significant difference in the biodistribution of either functionalized SWCNTs was observed in MRI. In vivo assessments revealed a statistically significant increase (p < 0.05) in oxidative stress as early as 24 h in serum and liver; however, all values normalized at 2 weeks’ investigation time point. DNA damage was minimal with either PEG-COOH or PEG-NH2 functionalized SWCNTs after 2 weeks’ exposure. The negatively charged SWCNTs caused lesser DNA damage compared to positively charged samples. Carboxy-functionalized SWCNTs did not cause substantial changes in inflammatory mediators and were found to be significantly safer than non-functionalized SWCNTs and may pave the way for novel biomedical applications in cancer diagnosis and therapy.

Glucose Oxidase Immobilized on a Functional Polymer Modified Glassy Carbon Electrode and Its Molecule Recognition of Glucose.

In the present study, a glucose oxidase (GluOx) direct electron transfer was realized on an aminated polyethylene glycol (mPEG), carboxylic acid functionalized multi-walled carbon nanotubes (fMWCNTs), and ionic liquid (IL) composite functional polymer modified glassy carbon electrode (GCE). The amino groups in PEG, carboxyl groups in multi-walled carbon nanotubes, and IL may have a better synergistic effect, thus more effectively adjust the hydrophobicity, stability, conductivity, and biocompatibility of the composite functional polymer film. The composite polymer membranes were characterized by cyclic voltammetry (CV), ultraviolet-visible (UV-Vis) spectrophotometer, fluorescence spectroscopy, electrochemical impedance spectroscopy (EIS), and transmission electron microscopy (TEM), respectively. In 50 mM, pH 7.0 phosphate buffer solution, the formal potential and heterogeneous electron transfer constant (ks) of GluOx on the composite functional polymer modified GCE were −0.27 V and 6.5 s−1, respectively. The modified electrode could recognize and detect glucose linearly in the range of 20 to 950 μM with a detection limit of 0.2 μM. The apparent Michaelis-Menten constant (Kmapp) of the modified electrode was 143 μM. The IL/mPEG-fMWCNTs functional polymer could preserve the conformational structure and catalytic activity of GluOx and lead to high sensitivity, stability, and selectivity of the biosensors for glucose recognition and detection.

DenTimol as A Dendrimeric Timolol Analogue for Glaucoma Therapy: Synthesis and Preliminary Efficacy and Safety Assessment.

In this work, we report the synthesis and characterization of DenTimol, a dendrimer-based polymeric timolol analog, as a glaucoma medication. A timolol precursor ( S)-4-[4-(oxiranylmethoxy)-1,2,5-thiadiazol-3-yl]morpholine (OTM) was reacted with the heterobifunctional amine polyethylene glycol acetic acid (amine-PEG-acetic acid, Mn = 2000 g/mol) via a ring opening reaction of an epoxide by an amine to form the OTM-PEG conjugate. OTM-PEG was then coupled to an ethylenediamine (EDA) core polyamidoamine (PAMAM) dendrimer G3 to generate DenTimol using the N-(3-(dimethylamino)propyl)- N'-ethylcarbodiimide hydrochloride (EDC)/ N-hydroxysuccinimide (NHS) coupling reaction. MALDI mass spectrometry, 1H NMR spectroscopy, and HPLC were applied to characterize the intermediate and final products. Ex vivo corneal permeation of DenTimol was assessed using the Franz diffusion cell system mounted with freshly extracted rabbit cornea. The cytotoxicity of DenTimol was assessed using the WST-1 assay. Our results show that DenTimol is nontoxic up to an OTM equivalent concentration of 100 μM. DenTimol is efficient at crossing the cornea. About 8% of the dendrimeric drug permeated through the cornea in 4 h. Its IOP-lowering effect was observed in normotensive adult Brown Norway male rats. Compared to the undosed eye, an IOP reduction by an average of 7.3 mmHg (∼30% reduction from baseline) was observed in the eye topically treated with DenTimol (2 × 5 μL, 0.5% w/v timolol equivalent) in less than 30 min. Daily dosing of DenTimol for a week did not cause any irritation or toxicity as confirmed by the histological examination of ocular tissues, including the cornea, ciliary body, and retina.

Carbohydrate-based electrochemical biosensor for detection of a cancer biomarker in human plasma

Autocrine motility factor (AMF) is a tumor-secreted cytokine that stimulates tumor cell motility in vitro and metastasis in vivo. AMF could be detected in serum or urine of cancer patients with worse prognosis. Reported as a cancer biomarker, AMF secretion into body fluids might be closely related to metastases formation. In this study, a sensitive and specific carbohydrate-based electrochemical biosensor was designed for the detection and quantification of a protein model of AMF, namely phosphoglucose isomerase from rabbit muscle (RmPGI). Indeed, RmPGI displays high homology with AMF and has been shown to have AMF activity. The biosensor was constructed by covalent binding of the enzyme substrate d-fructose 6-phosphate (F6P). Immobilization was achieved on a gold surface electrode following a bottom-up approach through an aminated surface obtained by electrochemical patterning of ethylene diamine and terminal amine polyethylene glycol chain to prevent non-specific interactions. Carbohydrate-protein interactions were quantified in a range of 10 fM to 100nM. Complex formation was analyzed through monitoring of the redox couple Fe2+/Fe3+ by electrochemical impedance spectroscopy and square wave voltammetry. The F6P-biosensor demonstrates a detection limit of 6.6 fM and high selectivity when compared to other non-specific glycolytic proteins such as d-glucose-6-phosphate dehydrogenase. Detection of protein in spiked plasma was demonstrated and accuracy of 95% is obtained compared to result obtained in PBS (phosphate buffered saline). F6P-biosensor is a very promising proof of concept required for the design of a carbohydrate-based electrochemical biosensor using the enzyme substrate as bioreceptor. Such biosensor could be generalized to detect other protein biomarkers of interest.

Study on the Effects of Humic and Fulvic Acids on Quantum Dot Nanoparticles Using Capillary Electrophoresis with Laser-Induced Fluorescence Detection

The increasing production and use of quantum dot (QD) nanoparticles have caused concerns on the possibility of contaminating the aquatic and terrestrial ecosystems with wastes that may contain QDs. Therefore, studies on the behavior of QDs upon interaction with components of the natural environment have become of interest. This study investigated the fluorescence and electrophoretic mobility of carboxylic or amine polyethylene glycol (PEG)-functionalized CdSe/ZnS QDs in the presence of two aquatic humic substances (HS), Suwannee River humic and fulvic acids, using capillary electrophoresis with laser-induced fluorescence detection. Results showed initial enhancement in fluorescence of QDs at the onset of the interaction with HS, followed by fluorescence quenching at longer exposure with HS (>30 min). It was also observed that the electrophoretic mobility of QDs increases with increasing concentration of HS, suggesting an increase in the ratio in charge to hydrodynamic size of the nanoparticles. To determine if the QDs degraded upon interaction with HS, the QD-HS mixtures were dialyzed to separate free Cd2+ from intact QDs, followed by analysis of the solutions using inductively coupled plasma-mass spectrometry. Results suggested that degradation of QDs in the presence of HS did not occur within the period of incubation.

Visualization and Optical Trapping of an Individual Submicrometer-Sized Assembly in Aqueous Solution: Aminated Polyethylene Glycol (PEG-A) Complexed with Palmitic Acid and DNA in Poly(ethylene glycol) (PEG) Solution

The present study reports the visualization and optical trapping of an individual submicrometer-sized assembly from synthetic polymers using a laser. The assembly was made of PA (palmitic acid) and PEG-A (amino pendant-containing poly(ethylene glycol)) labeled with FITC (fluorescein-5-isothiocyanate type I) at the ratio of PEG-A:FITC = 10:1. The individual submicrometer-sized assemblies were detected at a concentration 50 times lower than the critical aggregation concentration of the PEG-A/PA assembly expected by surface tension measurement. In addition, submicrometer-sized particles were prepared from individual DNA molecules, T4 DNA (166 kbp), in a poly(ethylene glycol) solution. These synthetic assemblies were successfully trapped and transported using a laser, as well as DNA particles. Finally, laser manipulation is shown to be an effective method to judge whether the pair interaction of submicrometer-sized objects is attractive or repulsive.