Short Polyethylene Glycol Research Articles

One step synthesis of SERS active colloidal gold nanoparticles by reduction with polyethylene glycol

The utility of polyethylene glycol (PEG) modified gold nanoparticles (GNPs) as novel drug carriers was comprehensively described in the last decade. We report a very effective, simple, one step and rapid synthesis method for stable, highly surface-enhanced Raman scattering (SERS) active gold colloids, by reduction and stabilization with short and long chain polyethylene glycol, PEG200 and PEG8000, respectively. Depending on the mixing rate during the synthesis, the mean size of the GNPs can be controlled between 15 and 60nm. The obtained colloids have been characterized by UV–vis spectroscopy, transmission electron microscopy (TEM), and SERS. TEM micrographs reveal spherical nanoparticles with an average diameter of 15nm, and polygonal particles with a mean size of 60nm for the gold colloid with the absorption maximum at 520nm and 562nm, respectively. The SERS activity of these new gold colloids is comparable to that of the conventional gold colloid obtained by citrate reduction, as shown by the SERS spectra of various analytes, using the 633 laser line.

Short PEG-Linkers Improve the Performance of Targeted, Activatable Monoclonal Antibody-Indocyanine Green Optical Imaging Probes

The ability to switch optical imaging probes from the quenched (off) to the active state (on) has greatly improved target to background ratios. The optimal activation efficiency of an optical probe depends on complete quenching before activation and complete dequenching after activation. For instance, monoclonal antibody-indocyanine green (mAb-ICG) conjugates, which are promising agents for clinical translation, are normally quenched, but can be activated when bound to a cell surface receptor and internalized. However, the small fraction of commonly used ICG derivative (ICG-Sulfo-OSu) can bind noncovalently to its mAb and is, thus, gradually released from the mAb leading to relatively high background signal especially in the liver and the abdomen. In this study, we re-engineered a mAb-ICG conjugate, (Panitumumab-ICG) using bifunctional ICG derivatives (ICG-PEG4-Sulfo-OSu and ICG-PEG8-Sulfo-OSu) with short polyethylene glycol (PEG) linkers. Higher covalent binding (70-86%) was observed using the bifunctional ICG with short PEG linkers resulting in less in vivo noncovalent dissociation. Panitumumab-ICG conjugates with short PEG linkers were able to detect human epidermal growth factor receptor 1 (EGFR)-positive tumors with high tumor-to-background ratios (15.8 and 6.9 for EGFR positive tumor-to-negative tumor and tumor-to-liver ratios, respectively, at 3 d postinjection).

The synthesis of 64Cu-chelated porphyrin photosensitizers and their tumor-targeting peptide conjugates for the evaluation of target cell uptake and PET image-based pharmacokinetics of targeted photodynamic therapy agents

Targeted photodynamic therapy (PDT) is necessary for preventing the side effects associated with PDT, such as photosensitivity caused by the distribution of photosensitizers into normal tissues. In the development of targeted PDT agents, a simple evaluation system of in vivo pharmacokinetics, as well as target cell uptake, is absolutely imperative. We hypothesized that (64)Cu chelation with porphyrin photosensitizer-biomacromolecule conjugates may become a simple and versatile labeling strategy for this purpose. Protoporphyrin IX (PPIX) and a bombesin (BBN) analog, that interacts with the gastrin-released peptide (GRP) receptor, were used as a photosensitizer and tumor-targeting peptide, respectively. Then, a conjugate of PPIX and BBN analog linked via short polyethylene glycol (PPIX-PEG6-BBN analog) was synthesized and used as a targeted PDT agent. In addition, a (64)Cu-chelated PPIX-PEG6-BBN analog was synthesized under optimized reaction conditions. Lastly, cell uptake study and PET image-based pharmacokinetic analyses of the PPIX-PEG6-BBN analog were carried out in a human prostate cancer cell line, PC-3, which highly expresses the GRP receptor, and PC-3 tumor-bearing mice. It was confirmed that degradation (thought to be based on radiolysis) occurs, and large amounts of (64)Cu-labeling compounds are wasted in the reaction mixture. Interestingly, the addition of ethanol into the reaction mixture provides an effective solution for this problem. As for cell uptake study, the [(64)Cu]PPIX-PEG6-BBN analog demonstrated significantly higher uptake for PC-3 cells than [(64)Cu]PPIX and, in addition, the uptake of [(64)Cu]PPIX-PEG6-BBN analog was significantly inhibited by adding excess cold BBN analog peptide. PET image-based pharmacokinetic evaluation revealed that [(64)Cu]PPIX-PEG6-BBN analog and [(64)Cu]PPIX rapidly accumulate into the liver and kidney, circulate in blood for a long time compared with normal peptides, and distribute at a low level in the tumor. This result suggested that in vivo biodistribution of PPIX-PEG6-BBN analog is mainly dependent on the lipophilicity of PPIX. Ex vivo measurements of radioactivity distribution after PET studies showed that although there was no remarkable difference in the tumor/skin ratio of radioactivity between [(64)Cu]PPIX-PEG6-BBN analog and [(64)Cu]PPIX, the pancreas (an organ that also expresses GRP receptors)/skin ratio was significantly higher in the case of [(64)Cu]PPIX-PEG6-BBN analog. We report on the successful synthesis of (64)Cu-chelated porphyrin photosensitizers and their tumor-targeting peptide conjugates under conditions in which radiolysis is suppressed. This labeling strategy with porphyrin photosensitizers may be of value for the rapid development of ideal targeted PDT agents.

Synthesis, Photophysics, Electrochemistry and Electrogenerated Chemiluminescence of PEG-Modified BODIPY dyes in Organic and Aqueous Solutions.

A set polyethylene glycol (PEG) appended BODIPY architectures (BOPEG1 - BOPEG3) have been prepared and studied in CH2Cl2, H2O:CH3CN (1:1) and aqueous solutions. BOPEG1 and BOPEG2 both contain a short PEG chain and differ in substitution about the BODIPY framework. BOPEG3 is comprised of a fully substituted BODIPY moiety linked to a PEG polymer that is roughly 13 units in length. The photophysics and electrochemical properties of these compounds have been thoroughly characterized in CH2Cl2 and aqueous CH3CN solutions. The behavior of BOPEG1 - BOPEG3 correlates with established rules of BODIPY stability based on substitution about the BODIPY moiety. ECL for each of these compounds was also monitored. BOPEG1, which is unsubstituted at the 2- and 6-positions dimerized upon electrochemical oxidation while BOPEG2, which contains ethyl groups at the 2- and 6-positions, was much more robust and served as an excellent ECL luminophore. BOPEG3 is highly soluble in water due to the long PEG tether and demonstrated modest ECL activity in aqueous solutions using tri-n-propylamine (TPrA) as a coreactant. As such, BOPEG3 represents the first BODIPY derivative that has been shown to display ECL in water without the need for an organic cosolvent, and marks an important step in the development of BODIPY based ECL probes for various biosensing applications.

Interparticle Dispersion, Membrane Curvature, and Penetration Induced by Single-Walled Carbon Nanotubes Wrapped with Lipids and PEGylated Lipids

Single-walled carbon nanotubes (SWNTs) wrapped with different types of lipids and polyethylene glycol (PEG)-grafted lipids were simulated with lipid bilayers. Simulations were carried out with the previously parametrized coarse-grained (CG) SWNT and PEG force fields that had captured the experimentally observed conformations of self-assembled SWNT-lipid complexes and phase behavior of PEG-grafted lipids. Simulations of multiple copies of the SWNT in water show that all pure SWNTs aggregate, lipid-wrapped SWNTs partially aggregate, but those wrapped with lipids grafted to PEG (M(w) = 550) completely disperse, indicating the effect of short PEG chains on interparticle aggregation, in agreement with experiment. Starting with initial SWNT orientation parallel to the bilayer surface, SWNTs wrapped with lysophospholipids and PEG (M(w) = 550)-grafted lipids insert into the hydrophobic region of the bilayer, while SWNTs wrapped with phospholipids and longer PEG (M(w) = 2000)-grafted lipids do not. These indicate that SWNTs insert because of the hydrophobic interaction with the bilayer tails, but the tight wrapping of charged lipid headgroups and long hydrophilic PEG chains can weaken the hydrophobic interaction and inhibit SWNT insertion. The inserted SWNTs contact the entire tails of neighboring lipids in one leaflet of the bilayer, which disorders the lipid bilayer and induces positive curvature. Our findings indicate that interparticle aggregation, SWNT penetration, and membrane curvature can be modulated by the SWNT-lipid structure and the PEG length.

The impact of PEGylation patterns on the in vivo biodistribution of mixed shell micelles

Polyethylene glycol (PEG)-ylation is a widely used strategy to fabricate nanocarriers with a long blood circulation time. Further elaboration of the contribution of the surface PEGylation pattern to biodistribution is highly desirable. We fabricated a series of polyion complex (PIC) micelles PEGylated with different ratios (PEG2k and PEG550). The plasma protein adsorption, murine macrophage uptake, and in vivo biodistribution with iodine-125 as the tracer were systematically studied to elucidate the impact of PEGylation patterns on the biodistribution of micelles. We demonstrated that the PEGylated micelles with short hydrophilic PEG chains mixed on the surface were cleared quickly by the reticuloendothelial system (RES), and the single PEG2k PEGylated micelles could efficiently prolong the blood circulation time and increase their deposition in tumor sites. The present study extends the understanding of the PEGylation strategy to further advance the development of ideal nanocarriers for drug delivery and imaging applications.

Molecular Dynamics Simulations of Pegylated Compounds in Dopc Lipid Bilayer

Lipids constitute the primary structural element of biological membrane and they play a central role in biochemical and biophysical processes of the cells. Because of their obvious biocompatibility, lipids and their derivatives are of great importance in pharmaceutical applications. Lipids can self-assemble into a variety of structures such as bilayers, micelles, and liposomes. Liposomes are the key structure for drug delivery because they can transport hydrophilic and hydrophobic compounds embedded in their interior and in the bilayer respectively. Liposomes are vulnerable to attack from the immune system and after a first adhesion to the proteins in the blood plasma they are recognized and removed from the blood. The circulation time of liposomes in the bloodstream can be prolonged using lipids with hydrophilic polymers attached to their headgroups, which form a protective steric barrier.In this study, we performed molecular dynamics simulations to analyze the effect of the Polyethylene glycol (PEG) as polymer coatings. Here we analyze different biophysical properties of the equilibrated mixed bilayers to determine how the presence of PEGylated compounds in varying chain lengths and concentration affects the lipid bilayer. Short PEG chains ( 20 PEG units) are more stable in the water phase and their aggregates do not show the tendency to diffuse from the water to the hydrophobic core of the lipid bilayer. These simulations reveal that PEG chain length is an important factor in the development of functionalized liposomes for drug delivery.

Compact Quantum Dots for Single-molecule Imaging

Single-molecule imaging is an important tool for understanding the mechanisms of biomolecular function and for visualizing the spatial and temporal heterogeneity of molecular behaviors that underlie cellular biology 1-4. To image an individual molecule of interest, it is typically conjugated to a fluorescent tag (dye, protein, bead, or quantum dot) and observed with epifluorescence or total internal reflection fluorescence (TIRF) microscopy. While dyes and fluorescent proteins have been the mainstay of fluorescence imaging for decades, their fluorescence is unstable under high photon fluxes necessary to observe individual molecules, yielding only a few seconds of observation before complete loss of signal. Latex beads and dye-labeled beads provide improved signal stability but at the expense of drastically larger hydrodynamic size, which can deleteriously alter the diffusion and behavior of the molecule under study. Quantum dots (QDs) offer a balance between these two problematic regimes. These nanoparticles are composed of semiconductor materials and can be engineered with a hydrodynamically compact size with exceptional resistance to photodegradation 5. Thus in recent years QDs have been instrumental in enabling long-term observation of complex macromolecular behavior on the single molecule level. However these particles have still been found to exhibit impaired diffusion in crowded molecular environments such as the cellular cytoplasm and the neuronal synaptic cleft, where their sizes are still too large 4,6,7. Recently we have engineered the cores and surface coatings of QDs for minimized hydrodynamic size, while balancing offsets to colloidal stability, photostability, brightness, and nonspecific binding that have hindered the utility of compact QDs in the past 8,9. The goal of this article is to demonstrate the synthesis, modification, and characterization of these optimized nanocrystals, composed of an alloyed HgxCd1-xSe core coated with an insulating CdyZn1-yS shell, further coated with a multidentate polymer ligand modified with short polyethylene glycol (PEG) chains (Figure 1). Compared with conventional CdSe nanocrystals, HgxCd1-xSe alloys offer greater quantum yields of fluorescence, fluorescence at red and near-infrared wavelengths for enhanced signal-to-noise in cells, and excitation at non-cytotoxic visible wavelengths. Multidentate polymer coatings bind to the nanocrystal surface in a closed and flat conformation to minimize hydrodynamic size, and PEG neutralizes the surface charge to minimize nonspecific binding to cells and biomolecules. The end result is a brightly fluorescent nanocrystal with emission between 550-800 nm and a total hydrodynamic size near 12 nm. This is in the same size range as many soluble globular proteins in cells, and substantially smaller than conventional PEGylated QDs (25-35 nm).

Compact Quantum Dots for Single-molecule Imaging

Single-molecule imaging is an important tool for understanding the mechanisms of biomolecular function and for visualizing the spatial and temporal heterogeneity of molecular behaviors that underlie cellular biology (1-4). To image an individual molecule of interest, it is typically conjugated to a fluorescent tag (dye, protein, bead, or quantum dot) and observed with epifluorescence or total internal reflection fluorescence (TIRF) microscopy. While dyes and fluorescent proteins have been the mainstay of fluorescence imaging for decades, their fluorescence is unstable under high photon fluxes necessary to observe individual molecules, yielding only a few seconds of observation before complete loss of signal. Latex beads and dye-labeled beads provide improved signal stability but at the expense of drastically larger hydrodynamic size, which can deleteriously alter the diffusion and behavior of the molecule under study. Quantum dots (QDs) offer a balance between these two problematic regimes. These nanoparticles are composed of semiconductor materials and can be engineered with a hydrodynamically compact size with exceptional resistance to photodegradation (5). Thus in recent years QDs have been instrumental in enabling long-term observation of complex macromolecular behavior on the single molecule level. However these particles have still been found to exhibit impaired diffusion in crowded molecular environments such as the cellular cytoplasm and the neuronal synaptic cleft, where their sizes are still too large (4,6,7). Recently we have engineered the cores and surface coatings of QDs for minimized hydrodynamic size, while balancing offsets to colloidal stability, photostability, brightness, and nonspecific binding that have hindered the utility of compact QDs in the past (8,9). The goal of this article is to demonstrate the synthesis, modification, and characterization of these optimized nanocrystals, composed of an alloyed HgxCd1-xSe core coated with an insulating CdyZn1-yS shell, further coated with a multidentate polymer ligand modified with short polyethylene glycol (PEG) chains (Figure 1). Compared with conventional CdSe nanocrystals, HgxCd1-xSe alloys offer greater quantum yields of fluorescence, fluorescence at red and near-infrared wavelengths for enhanced signal-to-noise in cells, and excitation at non-cytotoxic visible wavelengths. Multidentate polymer coatings bind to the nanocrystal surface in a closed and flat conformation to minimize hydrodynamic size, and PEG neutralizes the surface charge to minimize nonspecific binding to cells and biomolecules. The end result is a brightly fluorescent nanocrystal with emission between 550-800 nm and a total hydrodynamic size near 12 nm. This is in the same size range as many soluble globular proteins in cells, and substantially smaller than conventional PEGylated QDs (25-35 nm).

Coil-helix transition in poly(L-glutamic acid): Evidence for a 3-state non-cooperative process

A careful analysis of measurements of circular dichroism of poly(L-glutamic acid) (PGA) shows that the data can be very accurately described by introducing a third state for the PGA configuration, in addition to the helix and coil ones, and considering a simple equilibrium between these three states, without cooperativity. The third state is more conspicuous when high molecular weight polyethyleneglycol (PEG) is added. Excluded-volume effects shown by differences in the presence of short and long PEG chains suggest a direct interaction of PEG and PGA rather than an osmotic effect.

Systemic Delivery Systems of Angiogenic Gene by Novel Bubble Liposomes Containing Cationic Lipid and Ultrasound Exposure

Recently, we developed polyethyleneglycol (PEG)-modified liposomes (Bubble liposomes; BLs) entrapping ultrasound (US) gas and reported that the combination of BL and US exposure was an effective tool for the delivery of pDNA directly into skeletal muscles of an ischemic hindlimb model with local injection. To achieve gene delivery to deeper tissues, we attempted to prepare novel Bubble liposomes which were able to be loaded with pDNA and useful for systemic injection. We prepared BLs using cationic lipid and analyzed the interaction with the BLs and pDNA using flow cytometry. The solution of pDNA-loaded BLs (p-BLs) was further injected into the tail vein of hindlimb ischemia model mice, and transdermal US exposure was applied to ischemic hindlimb. The effects of transfection on angiogenic factors were investigated by real-time PCR. Blood flow was determined using a laser Doppler blood flow meter. The interaction with BLs and pDNA increased in the presence of DOTAP and short PEG chains and resulted in increased stability of pDNA in the serum. Transfection with pDNA encoding the bFGF gene using p-BLs and US induced various angiogenic factors and improved the blood flow. The gene delivery system into the ischemic hindlimb using the combination of p-BLs and US exposure could be an effective tool for angiogenic gene therapy via systemic injection.

Click Chemistry on Solution-Dispersed Graphene and Monolayer CVD Graphene

Graphene from two different preparative routes was successfully functionalized with 4-propargyloxybenzenediazonium tetrafluoroborate in order to study a subsequent attachment by click chemistry (1,3-dipolar azide–alkyne cycloaddition) of a short chain polyethylene glycol with terminal carboxylic end group (PEG-COOH). The reaction steps were studied by FTIR and Raman spectroscopies, as well as zeta-potential and surface tension measurements. In the first route, pristine graphene was surfactant dispersed from a stage controlled expanded graphite before reaction, resulting in colloidally stable dispersions after dialysis removal of the surfactant following the two functionalization steps. The chemistry was shown to increase the zeta-potential from −45.3 to −54.6 mV and increase the surface tension from 48.5 to 63.0 mN/m compared to those of the precursor solution. The magnitudes of the zeta-potential and the resulting solution concentration were shown to increase with grafting density up to 14.2 μg/mL. A col...

Design and potential application of PEGylated gold nanoparticles with size-dependent permeation through brain microvasculature

Gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provides a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood-brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, there are currently no studies that systematically examine brain microvasculature permeation of polyethylene glycol (PEG)-functionalized AuNPs. Such studies could pave the way for rationale AuNP design for passive targeting of malignant tumors. In this report we designed and characterized AuNPs with varying core particle sizes (4–24 nm) and PEG chain lengths [molecular weight 1000–10,000]. Using an in-vitro model designed to mimic the transport-permissive brain microvasculature, we demonstrate size-dependent permeation properties with respect to core particle size and PEG chain length. In general short PEG chain length (molecular weight 1000–2000) in combination with smallest core size led to optimum permeation in our model system. From the Clinical EditorIn this report the authors designed and characterized PEGylated gold NPs with varying core particle sizes and PEG chain lengths and demonstrate that short PEG chain length in combination with smallest core size led to optimum permeation of a blood-brain barrier model system. These findings may pave the way to optimized therapy of malignant brain tumors.

Dendrimer-based MRI contrast agents: the effects of PEGylation on relaxivity and pharmacokinetics

Polyethylene glycol (PEG) surface modification can make nanomaterials highly hydrophilic, reducing their sequestration in the reticuloendothelial system. In this study, polyamidoamine (PAMAM) dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated. Specifically, Gd chelate-bearing PAMAM dendrimers (generations 4 and 5; G4 and G5) were conjugated with two different PEG chains (2 kDa and 5 kDa; 2k and 5k). Long PEG chains (5k) on the smaller (G4) dendrimer resulted in reduced relaxivity compared to non-PEGylated dendrimers, whereas short PEG chains (2k) on a larger (G5) dendrimer produced relaxivities comparable to non-PEGylated G4 dendrimers. The relaxivity of all PEGylated or lysine-conjugated dendrimers increased at higher temperature, whereas that of intact G4 Gd-PAMAM dendrimer decreased. All PEGylated dendrimers had minimal liver and kidney uptake and remained in circulation for at least 1 hour. Thus, surface-PEGylated Gd-PAMAM dendrimers showed decreased plasma clearance and prolonged retention in the blood pool. Shorter PEG, higher generation conjugates led to higher relaxivity. From the Clinical EditorIn this study, polyamidoamine dendrimers bearing gadolinium (Gd) chelates were PEGylated with different PEG-chain lengths, and the effects on paramagnetic and pharmacokinetic properties were evaluated.

Different complex surfaces of polyethyleneglycol (PEG) and REDV ligand to enhance the endothelial cells selectivity over smooth muscle cells

Arg-Glu-Asp-Val (REDV) peptide with endothelial cells (ECs) selectivity was immobilized onto PEG based polymeric coating via the active p-nitrophenyloxycarbonyl group. The adhesion and proliferation of human umbilical vein endothelial cells (HUVECs) and human aortic smooth muscle cells (HASMCs) onto surface modified either by REDV end-tethered polyethylene glycol (PEG) or by the complex of free PEG and REDV were investigated to understand the synergic action of nonspecific resistance of PEG and specific recognitions of REDV. Cell culture results indicated that the surfaces end tethered by REDV peptide via PEG "spacer" (n=1, 6, 10) exhibited slight EC selectivity and showed small difference between different lengths of PEG chain. Both separate-culture and co-culture of HUVECs and HASMCs indicated that the introducing of free PEG into REDV tethered surface inhibited HASMCs adhesion significantly and remained a high level of HUVECs growth. Furthermore, the surface with short free PEG chain (n=6) was much more effective to enhance ECs selectivity than long EG chain (n=23). The combination of nonspecific resistance of short free PEG and the ECs selectivity of REDV peptide presents much better ability to enhance the competitive adhesion of HUVECs over HASMCs.

Polymer end-group mediated synthesis of well-defined catalytically active platinum nanoparticles

Simple, short polyethyleneglycol (PEG) chains were found to mediate the synthesis of well-defined 7–8nm cubic and truncated cubic platinum (Pt) particles that required only mild ligand removal conditions to yield highly active catalysts for the oxygen reduction reaction (ORR). FTIR analyses showed that only the hydroxyl end groups of the PEG chains associate with the platinum particles, which oxidize readily to form carbonyl groups with weaker interactions with the platinum surface. ORR analysis showed a mass activity of 50 μA μg−1 for the PEG synthesized Pt nanoparticles (NPs), as compared to a mass activity of 45 μA μg−1 for platinum black. The half-wave potentials of PEG Pt NPs and Pt black were found to be 427 mV and 529 mV, respectively, showing a high catalytic activity of PEG Pt NPs towards ORR. Well-defined particles were also produced from amine-terminated PEG, but as the amines could not be removed by simple acid washing, the ORR activity was greatly diminished. Since short low molecular weight PEG was found to control particle nucleation and growth predominantly through its end groups, this work demonstrates that PEG is a versatile scaffold from which to screen a wide variety of functional moieties, including biomolecules, as templates for complex nanoparticle synthesis.

Impact of the State of Water on the Dispersion Stability of a Skin Cream Formulation Elucidated by Magnetic Resonance Techniques

This study investigated the relationship between the state of water and the dispersion stability of a skin cream formulation. Hydrophilic ointments treated with a high-pressure wet-type jet mill were used as model formulations. Spin-lattice relaxation times (T(1)) were measured by magnetic resonance techniques to estimate the state of water in samples. A shorter T(1) relaxation time was obtained from samples with higher surfactant content, whereas the processing pressure of the jet mill and 1-week storage at 40 °C did not influence the T(1) relaxation time. Observations using scanning electron microscopy (SEM) showed that coalescence occurred in samples with lower surfactant contents (1.0% by weight) following 1-week storage at 40 °C. We also investigated samples prepared using a hydrophilic surfactant with a short polyethylene glycol (PEG) chain and with PEG-4000. From the change in T(1) relaxation times after removing the oil phase from samples by centrifugation, it was clarified that most of the surfactant was located on the surface of oil droplets. Furthermore, SEM observations showed that phase separation was facilitated as the PEG chain length of the surfactant shortened. Thus, a thin water layer over oil droplets is the most important factor for stabilizing their dispersion. This study provides proof-of-principle results on the contribution of the state of water to the dispersion stability of a skin cream formulation.

Effect of polyethylene glycol (PEG) length on the association properties of temperature-sensitive amphiphilic triblock copolymers (PNIPAAMm-b-PEGn-b-PNIPAAMm) in aqueous solution

Effects of temperature on the association behavior in aqueous solutions of a series of thermosensitive poly(N-isopropylacrylamide)-block-poly(ethylene glycol)-block-poly(N-isopropylacrylamide) triblock copolymers (PNIPAAMm-b-PEGn-b-PNIPAAMm) with the length of the PNIPAAM block fixed (m ≈ 67) and with different lengths of the PEG block (n = 23, 34, 77, and 165) have been studied with the aid of turbidity, dynamic light scattering (DLS), and Monte Carlo simulations. The turbidity results show that the sharp transition to high turbidity values is shifted to higher temperatures when the length of the PEG spacer is increased from 23 to 77, whereas no transition is observed for the longest PEG block. These findings are consistent with the DLS results, which suggest the formation of large association structures at temperatures well above the cloud point. The simulation results indicate that a long PEG-block portion separating the PNIPAAM blocks in the triblock copolymer reduces the tendency of the polymer forming interchain associations at elevated temperatures. Simulation shows that for a long PEG spacer, the copolymer moiety is rather extended even at high temperatures, whereas for copolymers with a short PEG length the thermoresponsive block copolymer undergoes a transition from an extended to a compact conformation.

Water-solubilisation and bio-conjugation of a red-emitting BODIPY marker

The synthesis and preliminary bio-conjugation studies of a novel water-soluble red-emitting di-styryl BODIPY dye are disclosed. Aggregation behaviour of this compound under physiological conditions was suppressed by specific introduction of a di-sulfonated peptide-based linker at the meso phenyl substituent, sultonated styryl arms and short polyethyleneglycol chains at the boron center. Thus, a good quantum yield of 22% in PBS for this red-emitting BODIPY was obtained. Introduction of an activated ester function enabled successful bio-conjugation to monoclonal antibodies and proteins.

Chlorotoxin Labeled Magnetic Nanovectors for Targeted Gene Delivery to Glioma

Glioma accounts for 80% of brain tumors and currently remains one of the most lethal forms of cancers. Gene therapy could potentially improve the dismal prognosis of patients with glioma, but this treatment modality has not yet reached the bedside from the laboratory due to the lack of safe and effective gene delivery vehicles. In this study we investigate targeted gene delivery to C6 glioma cells in a xenograft mouse model using chlorotoxin (CTX) labeled nanoparticles. The developed nanovector consists of an iron oxide nanoparticle core, coated with a copolymer of chitosan, polyethylene glycol (PEG), and polyethylenimine (PEI). Green fluorescent protein (GFP) encoding DNA was bound to these nanoparticles, and CTX was then attached using a short PEG linker. Nanoparticles without CTX were also prepared as a control. Mice bearing C6 xenograft tumors were injected intravenously with the DNA-bound nanoparticles. Nanoparticle accumulation in the tumor site was monitored using magnetic resonance imaging and analyzed by histology, and GFP gene expression was monitored through Xenogen IVIS fluorescence imaging and confocal fluorescence microscopy. Interestingly, the CTX did not affect the accumulation of nanoparticles at the tumor site but specifically enhanced their uptake into cancer cells as evidenced by higher gene expression. These results indicate that this targeted gene delivery system may potentially improve treatment outcome of gene therapy for glioma and other deadly cancers.