PEG Nanoparticle Research Articles

PEG-Grafted Graphene/PLLA Nanocomposites: Effect of PEG Chain Length on Crystallization Kinetics of PLLA.

Poly-l-lactic acid (PLLA) nanocomposites containing graphene oxide (GO), modified with different chain lengths of poly(ethylene glycol) (PEG) (400, 2000, and 10 000 g/mol), were prepared by solution casting. The effect of the PEG chain length and nanoparticle content (0.5, 1, and 1.5 wt %) on the nucleation, crystal growth rate, and overall crystallization rate, under isothermal conditions, was then evaluated. The results showed that, in samples containing GO modified with 400 g/mol of PEG, the nucleation density increased as a function of a modified nanoparticle concentration. In the case of the samples containing GO modified with PEG of a molar mass of either 2000 or 10 000 g/mol, the nucleation density exhibited a maximum at a concentration of 1 wt %. Furthermore, the addition of graphene oxide modified with poly(ethylene glycol) of a molar mass of 2000 g/mol resulted in the largest nucleation, fastest crystal growth, and highest overall crystallization rate, for all concentrations. The results were explained in light of the steric hindrance between the modified nanoparticles.

Targeting BMI-1 with PLGA\u2013PEG nanoparticle-containing PTC209 modulates the behavior of human glioblastoma stem cells and cancer cells

Despite advances in glioblastoma (GBM) treatments, current approaches have failed to improve the overall survival of patients. The oncogene BMI-1, a core member of the polycomb group proteins, is a potential novel therapeutic target for GBM. To enhance the efficacy and reduce the toxicity, PTC209, a BMI-1 inhibitor, was loaded into a PLGA–PEG nanoparticle conjugated with CD133 antibody (Nano-PTC209) and its effect on the behavior of human GBM stem-like cells (GSCs) and the human glioblastoma cell line (U87MG) was assessed. Nano-PTC209 has a diameter of ~ 75 nm with efficient drug loading and controlled release. The IC50 values of Nano-PTC209 for GSCs and U87MG cells were considerably lower than PTC209. Nano-PTC209 significantly decreased the viability of both GSCs and U87MG cells in a dose-dependent manner and caused a significant enhancement of apoptosis and p53 levels as well as inhibition of AKT and JNK signaling pathways. Furthermore, Nano-PTC209 significantly inhibited the migration ability, decreased the activity of metalloproteinase-2 and -9, and increased the generation of reactive oxygen species in both GSCs and U87MG cells. Our data indicate that PLGA–PEG nanoparticle conjugated with CD133 antibody could be an ideal nanocarrier to deliver PTC209 and effectively target BMI-1 for potential approaches in the treatment of GBM.

Surface-modified nanoparticle transport evaluated in a multistage model of ovarian cancer.

e18057 Background: A novel multi-stage model composed of ovarian cancer (SKOV-3) and fibroblast (MRC-5) cells was developed to provide a physiologically relevant in vitro platform to assess nanoparticle (NP) transport and aid in the development of more targeted clinical therapies. This multicellular ovarian tumor spheroid model is customized to the stages of ovarian cancer progression. The model leverages knowledge of these distinct stages in vivo to simulate their respective microenvironment, and thus provide a more accurate platform for evaluation of nanoparticle transport and drug delivery into ovarian tumor tissue. We hypothesized that alterations to the tumor microenvironment (TME) along with inclusion of a peptide-based scaffold (Puramatrix, PMX) to represent the site of metastasis, would lead to enhanced cell growth, migration and altered NP transport, which may be more indicative of the challenging transport conditions encountered in clinical ovarian cancer. Methods: In order to validate the in vitro model, tumor spheroid growth and invasion were evaluated while exposed to stromal cell activation and tissue hypoxia. MRC-5 activation was achieved via the TGF-ß1 mediated pathway, while tissue hypoxia was induced via incubation at 5% oxygen. PEG and MPG surface-modified NP transport was assessed in both stages of the model via confocal microscopy. Results: Consistent with in vivo observations in the ascites and site of distal metastasis, spheroids exposed to an activated stromal microenvironment were denser, more contractile and more invasive than their unactivated counterparts (p < 0.05). Additionally, hypoxic conditions, like those observed in the low pH environment of the ascites, resulted in negative spheroid radial growth over 5 days, compared to an increase for those cultured in normoxic conditions (p < 0.005). MPG-modified NPs exhibited superior tissue penetration relative to PEG-modified NPs in the ascites stage of the model (p < 0.05). Alternatively, PEG NPs enhanced penetration relative to MPG NPs when evaluated under metastatic conditions. In this case, NP transport was attenuated regardless of surface modification, due to the PMX-induced ECM reorganization. Conclusions: A novel multi-stage model, representative of ovarian cancer, was developed to evaluate NP transport in tumor tissue. We evaluated critical conditions in the microenvironment of ascites and metastasis and how these conditions may affect nanotherapy. Future studies will evaluate NP treatments by encapsulating a chemotherapeutic and measuring IC-50 values.

Length of surface PEG modulates nanocarrier transcytosis across brain vascular endothelial cells

Diblock PLA-PEG nanoparticles were produced to establish the role of PEG chain length on brain vascular endothelial cell transcytosis. 100-nm nanoparticles tagged with fluorescent pyrene butanol and coated with PEG chains (Mw: 1-10 kDa), at similar PEG surface density, were used to study endocytosis and transcytosis phenomena on mouse vascular endothelial cell monolayers. The transport mechanisms were then investigated through inhibitory processes. Our results show that there is an evident correlation between PEG chain length and nanoparticle translocation. The highest transcytosis rates were obtained with PEG5000 and PEG10000 and macropinocytosis appeared to play a central role in cell uptake. This study constitutes the first systematic exploration of the role of PEG chain length on nanoparticle endocytosis and transcytosis in an in vitro model of the blood–brain barrier.

Redox-responsive self-assembly PEG nanoparticle enhanced triptolide for efficient antitumor treatment

Chemotherapy induces tumor cell death by directly damaging DNA or hindering cell mitosis. Some of the drawbacks of most chemotherapy are lack of target selectivity to tumor cells, and adverse drug reaction, which limit the treatment intensity and frequency. Herein, we synthesized the prodrug of triptolide (TP) coupled to vitamin E (VE) using dithiodiglycolic acid and co-dissolved with PEG2000- linoleic acid (MPEG200-LD) in ethanol. The PEGylated TP prodrug self-assembly nanoparticles (PTPPSN) were prepared via nanoprecipitation method. Besides, characterization, stability and in vitro release of the PEGylated nanometer prodrug were investigated. Furthermore, in vitro and in vivo antitumor efficacy of PTPPSN explored showed that the cytotoxicity of triptolide was significantly reduced in vitro preparation. However, in vitro and in vivo antitumor effect of PTPPSN was significantly improved compared to the original triptolide. In summary, the PEGylated nanoparticle successfully encapsulated triptolide yielded suitable cell microenvironment, and nanotechnology-related achievements. This study, therefore, provides a new method for antitumor research as well as an innovative technology for clinical treatment of malignant tumor.

Core-interlayer-shell Fe3O4@mSiO2@lipid-PEG-methotrexate nanoparticle for multimodal imaging and multistage targeted chemo-photodynamic therapy

Multimodal imaging-guided multistage targeted synergistic combination therapy possesses many advantages including increased tumoricidal effect, reduced toxicity, and retarded drug resistance. Herein, we have elaborately developed a core-interlayer-shell structure Fe3O4@mSiO2@lipid-PEG-methotrexatenanoparticle(FMLM), in which the Fe3O4 core could be used for magnet-stimulate-response drug release, magnetic resonance imaging, and early-phase magnet targeting ability; the mSiO2 layer could encapsulate anticancer drug doxorubicin (Dox) for chemotherapy; and the protective shell of lipid-PEG and lipid-PEG-methotrexate offered later-phase specific cellular targeting ability, good water dispersibility, and loading of photosensitizer zinc phthalocyanine (ZnPc) for simultaneous near-infrared fluorescence imaging and photodynamic therapy. Both in vitro and in vivo studies indicated that the both Dox and ZnPc-loaded FMLM (Dox/ZnPc-FMLM) exhibited the enhanced tumor accumulation, increased cellular uptake, improved anticancer activity, and weaked side effects compared with Dox/ZnPc-Fe3O4@mSiO2@lipid-PEG nanoparticle (Dox/ZnPc-FML) and free drug. For the first time, magnet targeting cooperative with methotrexate macromolecular prodrug targeting is successfully exploited to develop a promising versatile theranostic nanoplatform for dual-modal fluorescence and magnetic resonance imaging-guided combined chemo-photodynamic cancer therapy.

Correction: PEGylated gold nanoparticles: polymer quantification as a function of PEG lengths and nanoparticle dimensions

Correction for ‘PEGylated gold nanoparticles: polymer quantification as a function of PEG lengths and nanoparticle dimensions’ by Kamil Rahme et al., RSC Adv., 2013, 3, 6085–6094.

Synthesis and Photophysical Characterization of Several 2,3-Quinoxaline Derivatives: An Application of Pd(0)/PEG Nanoparticle Catalyst for Sonogashira Coupling

ABSTRACTWe have reported synthesis of monoalkynyl- and dialkynyl-quinoxalines using Pd(0)/PEG nanoparticles as a catalyst and the tandem cyclization of the dialkynequinoxalines with sodium azide in high yields. The structures of all synthesized compounds were confirmed by IR, NMR and ESI-MS. The derivatives showed the absorption maxima at the region of 370 to 442 nm and emission maxima at the region of 386 to 539 nm with high fluorescence intensity in chloroform. It suggests that compounds 4b, 4c, 5b and 5c can be potential candidates for optical device applications.

Potential toxicity of up-converting nanoparticles encapsulated with a bilayer formed by ligand attraction.

The cellular toxicity of nanoparticles that were capped with a bilayered ligand was studied using an up-converting (UC) phosphor material as a representative nanoparticle (NP). The results indicate that although UC NPs are known to be nontoxic, the toxicity of the NPs depends strongly on ligand coordination conditions, in addition to the other commonly known parameters such as size, structure, surface charge etc. Oleate-capped hydrophobic NaYF4:Yb,Er NPs were surface modified to yield three extreme conditions: bare particles that were stripped of the oleate ligands; particles with covalently bound poly(ethylene glycol) (PEG) ligands; and particles with an bilayer of PEG-oleate ligands using the oleate surface group that was remained after synthesis. It was found that the bare particles and the covalent PEG NPs induced little toxicity. However, particles that were rendered biocompatible by forming a bilayer with an amphiphilic ligand (i.e., PEG-oleate) resulted in significant cell toxicity. These findings strongly suggest that the PEG-oleate group dissociated from the bilayered oleate-capped NPs, resulting in significant toxicity by exposing the hydrophobic oleate-capped NPs to the cell. Based on results with bare particles, the NaLnF4:Yb,Er (Ln = Y, Gd) up-converting phosphors are essentially less-toxic. Capping and functionalizing these particles with ligand intercalation may, however, not be a suitable method for rendering the NPs suitable for bioapplication as the ligand can potentially dissociate upon cellular interaction, leading to significant toxicity.

Silver–PEGylated dendrimer nanocomposite coating for anti-fouling thin film composite membranes for water treatment

This study proposes a facile method to fabricate thin film composite (TFC) membranes with silver–polyethylene glycol PEGylated dendrimer nanocomposite coatings on the surface to reduce both bacteria and protein fouling in the sustainable water treatment processes. Interestingly, the surfaces of TFC membranes have been imparted with different functionalities such as carboxylic acid, amine, PEG or silver nanoparticles in the modification process, which provide useful platforms to compare the anti-fouling properties of the four kinds of functional groups. Significant improvements on hydrophilicity have been found after modifications. All modified membranes show reduced attachment of E. coli and bovin serum albumin (BSA). Among them, the silver–PEGylated dendrimer nanocomposite membrane is subjected to the least fouling by the maximum fouling reduction of 99.8%. In particular, as a unique strength of this study, AFM force measurements were performed on membrane surfaces to study the interactions between protein and different surfaces. The adhesion force between the amine-functionalized surface and the tip suggests that the electrostatic interactions between the amine-modified membrane is very strong, resulting in a fast initial deposition of proteins on the membrane surface. The adhesion forces for PEG and silver nanoparticle modified membranes are small, which well explain the lower protein fouling of the membranes.

PEGylated gold nanoparticles: polymer quantification as a function of PEG lengths and nanoparticle dimensions

Au nanoparticles with diameters ranging between 15 and 170 nm have been synthesised in aqueous solution using a seed-mediated growth method, employing hydroxylamine hydrochloride as a reducing agent. Thiolated polyethylene glycol (mPEG-SH) polymers, with molecular weights ranging from 2100 to 51 000 g mol−1, were used as efficient particle stabilising ligands. Dynamic light scattering and zeta potential measurements confirmed that the overall mean diameter and zeta potential of the capped nanoparticles increased in a non-linear way with increasing molecular weight of the mPEG-SH ligand. Electron microscopy and thermal gravimetric analysis of the polymer-capped nanoparticles, with a mean gold core diameter of 15 nm, revealed that the grafting density of the mPEG-SH ligands decreased from 3.93 to 0.31 PEG nm−2 as the molecular weight of the ligands increased from 2100 to 51 400 g mol−1 respectively, due to increased steric hindrance and polymer conformational entropy with increase in the PEG chain length. Additionally, the number of bound mPEG-SH ligands, with a molecular weight of 10 800 g mol−1, was found to increase in a non-linear way from 278 (σ = 42) to approximately 12 960 PEG (σ = 1227) when the mean Au core diameter increased from 15 to 115 nm respectively. However, the grafting density of mPEG10 000-SH ligands was higher on 15 nm Au nanoparticles and decreased slightly from 1.57 to 0.8 PEG nm−2 when the diameter increased; this effect can be attributed to the fact that smaller particles offer higher surface curvature, therefore allowing increased polymer loading per nm2. Au nanoparticles were also shown to interact with CT-26 cells without causing noticeable toxicity.

An HPLC method for the pharmacokinetic study of vincristine sulfate-loaded PLGA–PEG nanoparticle formulations after injection to rats

The aim of this study is to develop a simple and applicable HPLC method for the detection of vincristine in rat plasma after administration of poly(lactic- co-glycolic acid)–poly(ethylene glycol) (PLGA–PEG) nanoparticles loaded with vincristine sulfate (VCR). Vincristine was extracted from rat plasma and vinblastine sulfate was chosen as the internal standard (IS). Chromatographic separation of VCR and IS was achieved by a Dikma Dimonsil C 18 column (200 mm × 4.6 mm) with the mobile phase consisting of 0.02 M sodium dihydrogen phosphate–methanol (36:64, v/v, pH = 4.7) at a flow rate of 1.0 mL/min. The ultraviolet detection wavelength was set at 276 nm. The calibration curve was linear over a concentration range of 0.05–5.0 μg/mL. The intra-day and inter-day accuracy for three quality controls (QC) samples was 93.48–107.74% and 92.61–96.58%, respectively; the precision was less than 9%. The average method recoveries for vincristine from spiked plasma at all QC levels were over 83%; and extraction recoveries were between 66 and 70%. Vincristine was stable in rat plasma for one month at −80 °C, for 8 h at room temperature, as well as during three freeze–thaw cycles. This HPLC method was applied successfully to the pharmacokinetic study of vincristine in rats after a single intravenous injection of VCR in physiological saline (F-VCR) solution, VCR-loaded PLGA–mPEG nanoparticles with (NP1) and PLGA–PEG–folate nanoparticles (NP2) suspension, respectively. There were significant differences in main pharmacokinetic parameters between F-VCR and the nanoparticles. Both kinds of VCR-loaded nanoparticles displayed improved pharmacokinetic profiles.

Preparation of monodisperse and size-controlled poly(ethylene glycol) hydrogel nanoparticles using liposome templates

Liposomes were used as templates to prepare size-controlled and monodisperse poly(ethylene glycol) (PEG) hydrogel nanoparticles. The procedure for the preparation of PEG nanoparticles using liposomes consists of encapsulation of photopolymerizable PEG hydrogel solution into the cavity of the liposomes, extrusion through a membrane with a specific pore size, and photopolymerization of the contents inside the liposomes by UV irradiation. The size distributions of the prepared particles were 1.32 ± 0.16 μm (12%), 450 ± 62 nm (14%), and 94 ± 12 nm (13%) after extrusion through membrane filters with pore sizes of 1 μm, 400 nm, and 100 nm, respectively. With this approach, it is also possible to modify the surface of the hydrogel nanoparticles with various functional groups in a one-step procedure. To functionalize the surface of a PEG nanoparticle, methoxy poly(ethylene glycol)–aldehyde was added as copolymer to the hydrogel-forming components and aldehyde-functionalized PEG nanoparticles could be obtained easily by UV-induced photopolymerization, following conjugation with poly- l-lysine-FITC through amine–aldehyde coupling. The prepared PEG particles showed strong fluorescence from FITC on the edge of the particles using confocal microscopy. The immobilization of biomaterials such as enzymes in hydrogel particles could be performed with loading β-galactosidases during the hydration step for liposome preparation without additional procedures. The resorufin produced by applying resorufin β- d-galactopyranoside as the substrate showed the fluorescence under the confocal microscopy.