Polyethylene Glycol Molecules Research Articles

Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors

The discovery of powerful genetic targets has spurred clinical development of gene therapy approaches to treat patients with malignant brain tumors. However, lack of success in the clinic has been attributed to the inability of conventional gene vectors to achieve gene transfer throughout highly disseminated primary brain tumors. Here, we demonstrate ex vivo that small nanocomplexes composed of DNA condensed by a blend of biodegradable polymer, poly(β-amino ester) (PBAE), with PBAE conjugated with 5kDa polyethylene glycol (PEG) molecules (PBAE-PEG) rapidly penetrate healthy brain parenchyma and orthotopic brain tumor tissues in rats. Rapid diffusion of these DNA-loaded nanocomplexes observed in fresh tissues ex vivo demonstrated that they avoided adhesive trapping in the brain owing to their dense PEG coating, which was critical to achieving widespread transgene expression throughout orthotopic rat brain tumors in vivo following administration by convection enhanced delivery. Transgene expression with the PBAE/PBAE-PEG blended nanocomplexes (DNA-loaded brain-penetrating nanocomplexes, or DNA-BPN) was uniform throughout the tumor core compared to nanocomplexes composed of DNA with PBAE only (DNA-loaded conventional nanocomplexes, or DNA-CN), and transgene expression reached beyond the tumor edge, where infiltrative cancer cells are found, only for the DNA-BPN formulation. Finally, DNA-BPN loaded with anti-cancer plasmid DNA provided significantly enhanced survival compared to the same plasmid DNA loaded in DNA-CN in two aggressive orthotopic brain tumor models in rats. These findings underscore the importance of achieving widespread delivery of therapeutic nucleic acids within brain tumors and provide a promising new delivery platform for localized gene therapy in the brain.

Abstract LB-129: NDAT and P-bi-TAT formulations of tetraiodothyroacetic acid (tetrac) induce devascularization, necrosis and apoptosis in glioblastoma xenografts

Abstract Thyroid hormone as L-thyroxine (T4) has been reported to stimulate proliferation of multiple glioma cell lines in vitro and there is clinical evidence that medical induction of hypothyroidism slows growth of glioblastoma multiforme (GBM). The proliferative action of T4 on glioma cells is initiated at a cell surface receptor for thyroid hormone on the extracellular domain of integrin αvβ3. Tetraiodothyroacetic acid (tetrac) is a thyroid hormone (T4) derivative that blocks T4 action at αvβ3 and has anticancer and anti-angiogenic activity. Tetrac has been covalently bonded via a linker to a nanoparticle (Nanotetrac, Nano-diamino-tetrac, NDAT) or to two polyethylene glycol (PEG) molecules (P-bi-TAT) that increase the potency of tetrac and broadens the anticancer properties of the drug. In the present studies of U87 MG GBM xenografts, NDAT administered daily for 10 days s.c. as 1 mg tetrac equivalent/kg reduced tumor xenograft weight at animal sacrifice by 50%, compared to untreated control lesions (p <0.01). Histopathological analysis of tumors revealed a 95% loss of the vascularity of treated tumors compared to controls at 10 days (p <0.001). There was no intratumoral hemorrhage. There was extensive cellular necrosis in treated tumors attributable to devascularization. Cells not necrotic in treated xenografts exhibited apoptosis, so that 80% of cells were either necrotic or apoptotic, compared to controls (p <0.001). Induction of apoptosis in cancer cells is a well-described quality of NDAT. P-bi-TAT treatment resulted in similar results after 20 days of treatment, but included a 21-day off-treatment follow-up after therapy. Xenografts achieved a 95% volume loss in the off-treatment, follow-up phase (P < 0.001). In summary, systemic NDAT and P-bi-TAT have been shown to be effective by multiple mechanisms in treatment of GBM xenografts. Citation Format: Paul J. Davis, Sudha Thangirala, Stewart Sell, Aleck Hercbergs, Shaker A. Mousa. NDAT and P-bi-TAT formulations of tetraiodothyroacetic acid (tetrac) induce devascularization, necrosis and apoptosis in glioblastoma xenografts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-129. doi:10.1158/1538-7445.AM2017-LB-129

TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMICS IN HEALTHY SUBJECTS OF SINGLE DOSES OF LY2599666, AN ANTIGEN BINDING FRAGMENT (FAB) OF A MONOCLONAL ANTIBODY THAT TARGETS SOLUBLE MONOMER Aβ LINKED TO A POLY(ETHYLENE GLYCOL) MOLECULE

Amyloid-beta (Aβ) antibody antigen-binding fragment (Fab)-polyethylene glycol (PEG), LY2599666, is a humanized, affinity-optimized monoclonal antibody Fab linked to a PEG molecule that targets soluble Aβ monomers. LY2599666 is engineered to support once-weekly (QW) subcutaneous (SC) dosing as a passive immunization therapy for Alzheimer's disease by attaching a 20 kDa PEG to the Fab to increase the half-life relative to the naked Fab. This first-in-human, subject- and investigator-blinded, placebo-controlled, single ascending dose study (NCT02614131) assessed the safety, tolerability, pharmacokinetics (PK), and pharmacodynamic (PD) effects of 10- to 200-mg SC doses of LY2599666 in healthy subjects. Four sequential cohorts of 10–11 subjects each, aged ≥ 20 years, were administered single doses of 10mg, 25mg, 100mg or 200mg LY2599666, respectively or matching placebo. Adverse events, vital signs, electrocardiograms, clinical laboratory tests, physical examinations, plasma PK, and plasma PD (plasma total Aβ) were assessed throughout the study and for up to 28 days after dosing. Forty-three heathy subjects received a SC dose of LY2599666 or placebo. Treatment-emergent adverse events reported regardless of treatment included injection-site erythema (5 subjects); dizziness (3 subjects); and contusion, headache, and upper respiratory tract infection (2 subjects each). Plasma free LY2599666 concentrations and Aβ concentrations (total Aβ 40 and total Aβ 42) will be presented. LY2599666 was generally well tolerated by healthy subjects after a single SC administration over a dose range of 10 to 200 mg.

A Core-Shell-Satellite Structured Fe3 O4 @g-C3 N4 -UCNPs-PEG for T1 /T2 -Weighted Dual-Modal MRI-Guided Photodynamic Therapy.

Reactive oxygen species (ROS) produced in the specific tumor site plays the key role in photodynamic therapy (PDT). Herein, a multifunctional nanoplatform is designed by absorbing ultrasmall upconversion nanoparticles (UCNPs) on mesoporous graphitic-phase carbon nitride (g-C3 N4 ) coated superparamagnetic iron oxide nanospheres, then further modified with polyethylene glycol (PEG)molecules (abbreviated as Fe3 O4 @g-C3 N4 -UCNPs-PEG). The inert g-C3 N4 layer between Fe3 O4 core and outer UCNPs can substantially depress the quenching effect of Fe3 O4 on the upconversion emission. Upon near-infrared (NIR) laser irradiation, the UCNPs convert the energy to the photosensitizer (g-C3 N4 layer) through fluorescence resonance energy transfer process, thus producing a vast amount of ROS. In vitro experiment exhibits an obvious NIR-triggered cell inhibition due to the cellular uptake of nanoparticles and the effective PDT efficacy. Notably, this platform is responsive to magnetic field, which enables targeted delivery under the guidance of an external magnetic field and supervises the therapeutic effect by T1 /T2 -weighted dual-modal magnetic resonance imaging. Moreover, in vivo therapeutic effect reveals that the magnetism guided accumulation of Fe3 O4 @g-C3 N4 -UCNPs-PEG can almost trigger a complete tumor inhibition without any perceived side effects. The experiments emphasize that the excellent prospect of Fe3 O4 @g-C3 N4 -UCNPs-PEG as a magnetic targeted platform for PDT application.

Modified headspace solid-phase microextraction for the determination of quantitative relationships between components of mixtures consisting of alcohols, esters, and ethers - impact of the vapor pressure difference of the compounds.

The quantitative relationship between analytes established by the headspace solid-phase microextraction procedure for multicomponent mixtures depends not only on the character and strength of interactions of individual components with solid-phase microextraction fiber but also on their vapor pressure in the applied headspace solid-phase microextraction system. This study proves that vapor pressure is of minor importance when the sample is dissolved/suspended in a low-volatility liquid of the same physicochemical character as that of the used solid phase microextraction fiber coating. It is demonstrated for mixtures of alcohols, esters, ethers and their selected representatives by applying a headspace solid-phase microextraction system composed of Carbowax fiber and sample solutions in polyethyleneglycol. The observed differences in quantitative relations between components of the examined mixtures established by their direct analysis and by modified headspace solid-phase microextraction are insignificant (Fexp <Fcrit ). It is explained by a significant diminution in vapor pressure difference between individual components of the examined mixture in the applied headspace solid phase microextraction system due to low components concentration in polyethyleneglycol suspensions (Raoult's law) and due to strong specific interactions of analyte molecules with polyethyleneglycol molecules.

Design and fabrication of covalently linked PEGylated nanohybrids of ZnO quantum dots with preserved and tunable fluorescence

Non-toxicity, high photo stability, biocompatibility and long lasting narrow emissions are some prime factors for an efficient biological marker. Unfortunately, commercial dyes and Cd-based fluorescent probes do not have such characteristics. Therefore, an efficient fluorescent probe is extremely desirable. Herein, functionalized ZnO quantum dots (QDs) and their nanohybrids with polyethylene glycol (PEG) were prepared by a room temperature solution growth tactic using 3-isocyanatopropyltriethoxysilane (3-ICPTES) as a coupling agent. Isocyanato functional groups were hosted on the surface of as prepared ZnO QDs by introducing optimized stoichiometric amounts of 3-ICPTES. The ZnO QDs were further bonded covalently to PEG via urethane linkages by the reaction of isocyanato functionalized ZnO QDs and hydroxyl groups from PEG molecules. The fluorescence was tuned from cyan to yellowish color after the functionalization of ZnO QDs with 3-ICPTES. Moreover, PEGylated nanohybrids showed greater water dispensability with photoluminescence preserved for at least six months. The present synthesis and coupling strategy for QDs may open up new ways to achieve biocompatible nanohybrids with higher stability and efficient luminescence for bio-imaging and biomedical applications.

Polyethylene glycol as an osmotic regulator in dough with reduced salt content

In this study, polyethylene glycol (PEG) was used as an osmotic regulator in dough to investigate the effects of reduced NaCl content on dough properties. The effects of water content (±10% of Farinograph absorption) and PEG's molar mass on dough machinability (stickiness, work of adhesion and cohesiveness) were estimated using a full factorial design. PEG with different molar masses (400, ∼1600, and 3350 g/mol) was added at a concentration of 1 g/100 g flour. All properties measured were affected significantly by the variation of water content and PEG's molar mass. At lower levels of dough hydration, stickiness increased with an increase in PEG's molar mass, whereas the opposite trend was observed at higher levels of dough hydration, suggesting there may be an optimum between the water restriction effect induced by PEG and dough's physical properties. The interaction effect was significant for both stickiness and work of adhesion, showing interdependence between water content, PEG molecule size and dough physical properties. The effects of PEG's concentration and molar mass on dough machinability were also assessed by full factorial design. Increasing PEG's molar mass and concentration improved dough machinability, that is, dough with reduced stickiness was obtained.

Specific targeting of human epidermal growth factor receptor 2 (HER2) overexpressing breast cancer cells by polyethylene glycol-grafted polyethyleneimine modified with anti-HER2 single-domain antibody

Polyethyleneimine is one of the most efficient non-viral gene delivery agents. However, some limitations such as non-specific cell binding, interactions with blood components, and relatively high cytotoxicity restrict its in vivo applications. In order to improve the properties of this molecule as a gene transfection vector, in this study, we developed a nano-carrier system based on polyethyleneimine derivatives synthesized by grafting bi-functional polyethylene glycol molecules (MAL-PEG3500-NHS) to 25 kDa branched polyethyleneimine polymer at three different molar ratios of 10, 20, and 30 (polyethylene glycol:polyethyleneimine). Variable domain of heavy-chain antibody against human epidermal growth factor receptor 2 as targeting agent was conjugated to polyethylene glycol–polyethyleneimine copolymer. In order to find the most effective resultant conjugate, the effect of these modifications on physicochemical properties, cytotoxicity, cellular uptake, and gene transfection efficiency of polyethyleneimine polymer was evaluated. According to the findings of this study and compared to unconjugated polyethyleneimine, PEGylated polyethyleneimine copolymers exhibit lower in vitro cytotoxicity. Polyethylene glycol–polyethyleneimine copolymer conjugated at a molar ratio of 10:1 (polyethylene glycol:polyethyleneimine) demonstrated a low cytotoxicity effect and desirable physicochemical properties. Anti-human epidermal growth factor receptor 2 variable domain of heavy-chain antibody conjugation further reduced the cytotoxicity of unmodified polyethyleneimine in all cell lines studied by 1.5- to 2-folds and also resulted in higher cellular uptake and transfection ability of this copolymer in human epidermal growth factor receptor 2 overexpressing breast cancer cell lines versus normal breast cells or human epidermal growth factor receptor 2 negative cell lines. Altogether, our data suggested that variable domain of heavy-chain antibody–polyethylene glycol–polyethyleneimine copolymers might be an efficient nano-carrier system for specific targeting of human epidermal growth factor receptor 2 expressing tumors.

Capsaicin-loaded folic acid-conjugated lipid nanoparticles for enhanced therapeutic efficacy in ovarian cancers.

In this study, folic acid-conjugated lipid nanoparticles were successfully prepared to enhance the active targeting of capsaicin (CAP) in ovarian cancers. The particles were nanosized and exhibited a controlled release of drug in the physiological conditions. The folic acid (FA)-conjugated system exhibited a remarkably higher uptake of nanoparticles in the cancer cells compared to that of non-targeted system. The folate-conjugated CAP-loaded lipid nanoparticles (CFLN) upon interacting with cancer cells were internalized via receptor-mediated endocytosis mechanism and resulted in higher concentration in the cancer cells. Consistently, CFLN showed a remarkably higher toxic effect compared to that of non-targeted nanoparticle system. CFLN showed significantly higher cancer cell apoptosis with nearly 39% of cells in apoptosis chamber (early and late) compared to only ∼21% and ∼11% for CAP-loaded lipid nanoparticles (CLN) and CAP. The loading of drug in the lipid nanoparticle system extended the drug retention in the blood circulation and allowed the active targeting to specific cancer cells. The prolonged circulation of drug attributed to the antifouling property of polyethylene glycol molecule in the structure. Overall, study highlights that using targeting moiety could enhance the therapeutic response of nanomedicines in the treatment of solid tumors.

Dispersion stability of nano-Sb2O3 particles modified with polyethylene glycol

ABSTRACTThe surface of nano-Sb2O3 particles was modified with polyethylene glycol (PEG) using the mechanochemical method, and the dispersion mechanism of modified nano-Sb2O3 particles was also discussed. The modified nano-Sb2O3 particles were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermal analysis (TGA) and UV absorbance. The results showed that the surface of nano-Sb2O3 particles was successfully coated by PEG molecules through the effect of hydrogen bonding, and the dispersion of nano-Sb2O3 particles in ethyl alcohol (C2H5OH) was significantly improved. Due to the different adsorption conformations of PEG molecules, the dispersion stability of nano-Sb2O3 particles was gradually improved with the increase of PEG average molecular weight and concentration. However, the superfluous PEG molecules would weaken the dispersion stability of nano-Sb2O3 particles.

Xenotransplantation of layer-by-layer encapsulated non-human primate islets with a specified immunosuppressive drug protocol

Islet transplantation is as effective as but also less immunogenic than pancreas transplantation for the treatment of type 1 diabetes mellitus. However, as the complete elimination of immunogenicity still remains a major obstacle in islet transplantation, layer-by-layer encapsulation (LbL) of pancreatic islets using biocompatible polymers offers a rational approach to reducing host immune response towards transplanted islets. We investigated the effect of LbL of non-human primate (NHP) islets on reducing immunogenicity as a preclinical model since NHPs have close phylogenetic and immunological relationship with humans. LbL with three-layers of polyethylene glycol (PEG) molecules (SH-6-arm-PEG-NHS, 6-arm-PEG-catechol and linear PEG-SH) showed a uniform nano-shielding on islets without the loss of viability or function of islets. An immunosuppressive drug protocol was also combined to improve the survival rate of the transplanted islets in vivo. A xenorecipient (C57BL/6 mice) of LbL islet transplanted along with our immunosuppressive drug protocol showed 100% survival rate for 150days after transplantation. On the other hand, naked islet recipients showed poor survival time of 5.5±1.4days without drugs and 77.5±42days with the drug protocol. Immunohistochemistry of the transplanted grafts and serum cytokine concentration demonstrated less immunogenicity in the LbL islet transplanted recipients compared with the naked islet ones.

AN EVALUATION OF OSMOTIC TECHNIQUE UNDER ULTRAVIOLET GERMICIDAL IRRADIATION EXPOSURE

The osmotic technique, which uses polyethylene glycol (PEG) solutions of varying concentrations with semipermeable membranes of different molecular weight cutoffs (MWCO), is commonly used to apply suction in soils. Cellulose acetate membranes which are most commonly used, are susceptible to microbial attacks. This in turn will lead to the intrusion of PEG into soil specimens. Osmotic and vapour equilibrium techniques are often used to establish drying suction-water content soil-water characteristic curves (SWCC). In this study, suctions of 0.11 to 300 MPa were applied on Andrassy bentonite slurries. At higher applied suctions, the osmotic tests were carried under short length ultraviolet germicidal irradiation (UVGI). In addition, Atomic Force Microscopy (AFM) and Fourier Infrared (FTiR) were employed to evaluate the changes in the semipermeable membranes and PEG molecules, respectively. The water content of the clay obtained from the osmotic tests was found to be greater at the overlapping suction region. Interestingly, under UVGI exposure, the water content was found to be in good agreement with the water content determined using the osmotic technique at low suctions and the vapour equilibrium technique at higher suctions. FTiR spectrum and AFM results revealed that some changes had occurred on both the PEG and in the membrane pore sizes. However, these changes did not affect the final water content in the bentonite and therefore, more precise suction-water content SWCC for the clay could be established.

Novel pegylated interferon-β as strong suppressor of the malignant ascites in a peritoneal metastasis model of human cancer.

Malignant ascites manifests as an end‐stage event during the progression of a number of cancers and lacks a generally accepted standard therapy. Interferon‐β (IFN‐β) has been used to treat several cancer indications; however, little is known about the efficacy of IFN‐β on malignant ascites. In the present study, we report on the development of a novel, engineered form of human and murine IFN‐β, each conjugated with a polyethylene glycol molecule (PEG‐hIFN‐β and PEG‐mIFN‐β, respectively). We provide evidence that these IFN‐β molecules retain anti‐viral potency comparable to unmodified IFN‐β in vitro and manifested improved pharmacokinetics in vivo. Interestingly, PEG‐mIFN‐β significantly inhibited the accumulation of ascites fluid and vascular permeability of the peritoneal membrane in models of ovarian cancer and gastric cancer cell xenograft mice. We further show that PEG‐hIFN‐β directly suppresses VEGF 165‐induced hyperpermeability in a monolayer of human vascular endothelial cells and that PEG‐mIFN‐β enhanced gene expression for a number of cell adhesion related molecules in mouse vascular endothelial cells. Taken together, these findings unveil a hitherto unrecognized potential of IFN‐β in maintaining vascular integrity, and provide proof‐of‐mechanism for a novel and long‐acting pegylated hIFN‐β for the therapeutic treatment of malignant ascites.

Click-PEGylation – A mobility shift approach to assess the redox state of cysteines in candidate proteins

The redox state of cysteine thiols is critical for protein function. Whereas cysteines play an important role in the maintenance of protein structure through the formation of internal disulfides, their nucleophilic thiol groups can become oxidatively modified in response to diverse redox challenges and thereby function in signalling and antioxidant defences. These oxidative modifications occur in response to a range of agents and stimuli, and can lead to the existence of multiple redox states for a given protein. To assess the role(s) of a protein in redox signalling and antioxidant defence, it is thus vital to be able to assess which of the multiple thiol redox states are present and to investigate how these alter under different conditions. While this can be done by a range of mass spectrometric-based methods, these are time-consuming, costly, and best suited to study abundant proteins or to perform an unbiased proteomic screen. One approach that can facilitate a targeted assessment of candidate proteins, as well as proteins that are low in abundance or proteomically challenging, is by electrophoretic mobility shift assays. Redox-modified cysteine residues are selectively tagged with a large group, such as a polyethylene glycol (PEG) polymer, and then the proteins are separated by electrophoresis followed by immunoblotting, which allows the inference of redox changes based on band shifts. However, the applicability of this method has been impaired by the difficulty of cleanly modifying protein thiols by large PEG reagents. To establish a more robust method for redox-selective PEGylation, we have utilised a Click chemistry approach, where free thiol groups are first labelled with a reagent modified to contain an alkyne moiety, which is subsequently Click-reacted with a PEG molecule containing a complementary azide function. This strategy can be adapted to study reversibly reduced or oxidised cysteines. Separation of the thiol labelling step from the PEG conjugation greatly facilitates the fidelity and flexibility of this approach. Here we show how the Click-PEGylation technique can be used to interrogate the redox state of proteins.

Modification of Nanoporous Silicon Nitride with Stable and Functional Organic Monolayers.

This study describes the formation of functional organic monolayers on thin, nanoporous silicon nitride membranes. We demonstrate that the vapor-phase carbene insertion into the surface C-H bonds can be used to form sub-5 nm molecular coatings on nanoporous materials, which can be further modified with monolayers of polyethylene glycol (PEG) molecules. We investigate composition, thickness, and stability of the functionalized monolayers and the changes in the membrane permeability and pore size distribution. We show that, due to the low coating thickness (~7 nm), the functionalized membrane retains 80% of the original gas permeance and 40% of the original hydraulic permeability. We also show that the carbene/PEG functionalization is hydrolytically stable for up to 48 h of exposure to water and that it can suppress nonspecific adsorption of the proteins BSA and IgG. Our results suggest that the vapor-phase carbenylation can be used as a complementary technology to the traditional self-assembly and polymer brush chemistries in chemical functionalization of nanoporous materials, which are limited in their ability to serve as stable coatings that do not occlude nanomembrane pores.

Advances in the treatment of relapsing&amp;ndash;remitting multiple sclerosis: the role of pegylated interferon &amp;beta;-1a

Multiple sclerosis (MS) is a progressive, neurodegenerative disease with unpredictable phases of relapse and remission. The cause of MS is unknown, but the pathology is characterized by infiltration of auto-reactive immune cells into the central nervous system (CNS) resulting in widespread neuroinflammation and neurodegeneration. Immunomodulatory-based therapies emerged in the 1990s and have been a cornerstone of disease management ever since. Interferon β (IFNβ) was the first biologic approved after demonstrating decreased relapse rates, disease activity and progression of disability in clinical trials. However, frequent dosing schedules have limited patient acceptance for long-term therapy. Pegylation, the process by which molecules of polyethylene glycol are covalently linked to a compound, has been utilized to increase the half-life of IFNβ and decrease the frequency of administration required. To date, there has been one clinical trial evaluating the efficacy of pegylated IFN. The purpose of this article is to provide an overview of the role of IFN in the treatment of MS and evaluate the available evidence for pegylated IFN therapy in MS.

Performance of Doxorubicin-Conjugated Gold Nanoparticles: Regulation of Drug Location

Drug-conjugated gold nanoparticles (GNPs), which are generally constructed with many molecules of thiol-terminated polyethylene glycol (PEG)-drug decorated on their surfaces via a thiol-Au covalent bond, are promising and efficient nanoprodrugs. However, because of the exposure of the hydrophobic drug molecules on the surface of the conjugate, in vivo stability, opsonization, and subsequent inefficient therapy become the main issues of this system. To solve these problems without complicating the structures of gold conjugates, herein we propose a method to change the relative position of PEG and the drug. A novel gold conjugate (GNP-NHN═Dox-mPEG) with doxorubicin (Dox) shielded by PEGylation on the surface of GNPs is designed. It demonstrates improved solubility, stability, and dispersion and achieves a two-step stimulus-responsive drug release in response to an acidic environment in lysosomes and then esterase in the cytoplasm. This unique manner of release enables the cytoplasm to act as a reservoir for sustained drug delivery into the nucleus to improve antitumor efficacy in vivo. The intratumoral drug concentrations of the conjugate reach 14.4 ± 1.4 μg/g at 8 h, a two-fold increase in the drug concentration compared with that of the doxorubicin hydrochloride group. This molecular design and regulation approach is facile but important in modulating the in vivo performance of nanovehicles and demonstrates its vital potential in developing effective nanoparticle-based drug delivery agents.

Effect of temperature on the synthesis of silver nanoparticles with polyethylene glycol: new insights into the reduction mechanism

Polyethylene glycol (PEG) molecules act as a reducing and stabilizing agent in the formation of silver nanoparticles. PEG undergoes thermal oxidative degradation at temperatures over 70 °C in the presence of oxygen. Here, we studied how the temperature and an oxidizing atmosphere could affect the synthesis of silver nanoparticles with PEG. We tested different AgNO3 concentrations for nanoparticles syntheses using PEG of low molecular weight, at 60 and 100 °C. At the higher temperature, the reducing action of PEG increased and the effect of PEG/Ag+ ratio on nanoparticles aggregation changed. These results suggest that different synthesis mechanisms operate at 60 and 100 °C. Thus, at 60 °C the reduction of silver ions can occur through the oxidation of the hydroxyl groups of PEG, as has been previously reported. We propose that the thermal oxidative degradation of PEG at 100 °C increases the number of both, functional groups and molecules that can reduce silver ions and stabilize silver nanoparticles. This degradation process could explain the enhancement of PEG reducing action observed by other authors when they increase the reaction temperature or use a PEG of higher molecular weight

A Microfabricated 96-Well 3D Assay Enabling High-Throughput Quantification of Cellular Invasion Capabilities

This paper presents a 96-well microfabricated assay to study three-dimensional (3D) invasion of tumor cells. A 3D cluster of tumor cells was first generated within each well by seeding cells onto a micro-patterned surface consisting of a central fibronectin-coated area that promotes cellular attachment, surrounded by a poly ethylene glycol (PEG) coated area that is resistant to cellular attachment. Following the formation of the 3D cell clusters, a 3D collagen extracellular matrix was formed in each well by thermal-triggered gelation. Invasion of the tumor cells into the extracellular matrix was subsequently initiated and monitored. Two modes of cellular infiltration were observed: A549 cells invaded into the extracellular matrix following the surfaces previously coated with PEG molecules in a pseudo-2D manner, while H1299 cells invaded into the extracellular matrix in a truly 3D manner including multiple directions. Based on the processing of 2D microscopic images, a key parameter, namely, equivalent invasion distance (the area of invaded cells divided by the circumference of the initial cell cluster) was obtained to quantify migration capabilities of these two cell types. These results validate the feasibility of the proposed platform, which may function as a high-throughput 3D cellular invasion assay.

Largely improved electromechanical properties of thermoplastic polyurethane dielectric elastomers by the synergistic effect of polyethylene glycol and partially reduced graphene oxide

In this study, moderate content of polyethylene glycol (PEG) with ionic conductivity and low content of graphene oxide (GO) were simultaneously introduced into thermoplastic polyurethane (TPU) followed by in-situ chemical reduction of GO (rGO) to prepare TPU/PEG/rGO dielectric elastomer (DE) composites with largely improved electromechanical performance. The results showed that PEG remarkably disrupted the hydrogen bonds between TPU chains in TPU/PEG/rGO composites and formed new hydrogen bonds with TPU. In addition, PEG molecules can also form hydrogen bonds with rGO, leading to the coating of PEG on GO and thus the separation of rGO from TPU. Interestingly, PEG and rGO showed significant synergistic effect on the dielectric constant (ε′) of the composites, resulting in the large increase in ε′ at 103 Hz from 7 for pristine TPU to 71 for TPU/PEG/rGO composite. This was attributed to the increase in dipole polarizability of TPU chains caused by the disruption of hydrogen bonds and the increase in interfacial polarizability caused by the favorable electron transfer from partially reduced GO coated by PEG to TPU. The elastic modulus (Y) of the TPU/PEG/rGO composites largely decreased because of the plasticizing effect of PEG and the separation of GO from TPU. Owing to the simultaneous increase in ε′ and decrease in Y, the composite showed 49 times increase in electromechanical sensitivity (β) and 6.5 times increase in actuated strain at a certain electric field over that of pristine TPU.