Amine-terminated Poly Ethylene Glycol Research Articles

Improvement of biological and corrosion behavior of plasma electrolytic oxidized Mg implant by 3D printed scaffold of amine-terminated PEG/PCL loaded with dexamethasone

Although magnesium-based implants have good biocompatibility and biodegradability, they suffer from rapid corrosion in the body environment, which limits their biomedical applications. This study represents an approach for designing a bioactive and anti-corrosive hybrid structure composed of an inorganic layer by plasma electrolytic oxidation process and an organic layer of 3D printed polycaprolactone and amine-terminated polyethylene glycol scaffold containing dexamethasone. The results indicated that the hybrid layer exhibited superior adhesion strength, high corrosion resistance, remarkable biocompatibility, cell attachment, and osteogenic differentiation. The dexamethasone released from the 3D printed scaffold revealed high osteogenic differentiation capability. Hence, the fabrication of plasma electrolytic oxidized interlayer with a 3D printed scaffold can be a novel platform to preserve the magnesium-based biological implants from corrosion and to regenerate bone along with the controlled release of osteogenic components.

A first-in-class dual-chelator theranostic agent designed for use with imaging-therapy radiometal pairs of different elements.

A covalent adduct of DFOB and DOTA separated by a l-lysine residue (DFOB-l-Lys-N 6-DOTA) exhibited remarkable regioselective metal binding, with {1H}-13C NMR spectral shifts supporting Zr(iv) coordinating to the DFOB unit, and Lu(iii) coordinating to the DOTA unit. This first-in-class, dual-chelator theranostic design could enable the use of imaging-therapy radiometal pairs of different elements, such as 89Zr for positron emission tomography (PET) imaging and 177Lu for low-energy β--particle radiation therapy. DFOB-l-Lys-N 6-DOTA was elaborated with an amine-terminated polyethylene glycol extender unit (PEG4) to give DFOB-N 2-(PEG4)-l-Lys-N 6-DOTA (compound D2) to enable installation of a phenyl-isothiocyanate group (Ph-NCS) for subsequent monoclonal antibody (mAb) conjugation (mAb = HuJ591). D2-mAb was radiolabeled with 89Zr or 177Lu to produce [89Zr]Zr-D2-mAb or [177Lu]Lu-D2-mAb, respectively, and in vivo PET/CT imaging and in vivo/ex vivo biodistribution properties measured with the matched controls [89Zr]Zr-DFOB-mAb or [177Lu]Lu-DOTA-mAb in a murine LNCaP prostate tumour xenograft model. The 89Zr-immuno-PET imaging function of [89Zr]Zr-D2-mAb and [89Zr]Zr-DFOB-mAb showed no significant difference in tumour accumulation at 48 or 120 h post injection. [89Zr]Zr-D2-mAb and [177Lu]Lu-D2-mAb showed similar ex vivo biodistribution properties at 120 h post-injection. Tumour uptake of [177Lu]Lu-D2-mAb shown by SPECT/CT imaging at 48 h and 120 h post-injection supported the therapeutic function of D2, which was corroborated by similar therapeutic efficacy between [177Lu]Lu-D2-mAb and [177Lu]Lu-DOTA-mAb, both showing a sustained reduction in tumour volume (>80% over 65 d) compared to vehicle. The work identifies D2 as a trifunctional chelator that could expand capabilities in mixed-element radiometal theranostics to improve dosimetry and the clinical outcomes of molecularly targeted radiation.

In situ forming of PEG-NH2/dialdehyde starch Schiff-base hydrogels and their application in slow-release urea

In this study, a biodegradable Schiff-base hydrogel urea, possessing substantial water retention and certain slow-release ability was designed and synthesized. Firstly, dialdehyde starch (DAS) and amine-terminated polyethylene glycol (PEG-(NH2)2) were synthesized using potato starch and polyethylene glycol. Then, a novel Schiff-base hydrogel (SH) was prepared through the in-situ reaction between the aldehyde group of DAS and the amino group of PEG-(NH2)2. Three SH based slow-release urea, designated as SHU1, SHU2, and SHU3 and distinguished by varying urea content, were obtained using SH as the substrate. Several characterizations and tests were conducted to determine the structure, thermal properties, morphology, swelling properties, sustainable use, water retention, and biodegradation properties of SH. Additionally, the slow-release behavior of SHU was studied. SEM results revealed that SH possessed a porous three-dimensional network structure, with a maximum water absorption capacity of 4440 % ± 6.23 %. Compared to pure urea, SHU exhibited better slow-release performance after 30 days of release in soil, with SHU1 having a residual nitrogen content of specifically 36.01 ± 0.57 % of the initial nitrogen content. A pot experiment with pakchoi substantiated the water retention and plant growth promotion properties of SHU. This study demonstrated a straightforward method for the preparation of starch-based Schiff-base hydrogels as fertilizer carriers.

Development of injectable hydrogels based on human amniotic membrane and polyethyleneglycol-modified nanosilicates for tissue engineering applications

Recently, decellularized amniotic membrane-derived hydrogels (DAMHs) have received significant attention for wound care, ocular surface reconstruction, and chondral healing. Despite the advantages of DAMHs for tissue engineering (TE), the loss of structural components during the decellularization process mitigates their mechanical strength and thus limits their practical application. Herein, we present a method for the surface modification of two-dimensional nanosilicates (laponite) as a rheological modifier to tailor the properties of DAMHs. Results show that after introducing nanosilicates, severe aggregation of the nanoparticles occurs, owing to the shielding effect of ions on the surface and edges of laponite. Loose interactions between the hydrophobic nanosilicate tactoids and hydrophilic polymer form laminated clay clusters surrounded by collagen fibers. At a high concentration of laponite (1:1 w/w), liquid-solid phase separation may also occur. A decreased storage modulus (up to 80 %), swelling ratio (up to 50 %), and gelation rate (up to 16 %) are thus attained. Electrosteric stabilization of the nanosilicates with amine-terminated polyethyleneglycol (AT-PEG) prevents aggregation of the nanosilicate in the hydrogel matrix and provides uniform distribution. As a result, most of the impaired physicomechanical properties are resolved.In vitrocell studies also determine that the AT-PEG modified nanosilicate-DAMHs exhibit higher cell viability and cell adhesion. The results of this research can pave the way toward developing injectable DAMHs with improved properties for TE.

Intra-articular Injection of Kartogenin-Enhanced Bone Marrow–Derived Mesenchymal Stem Cells in the Treatment of Knee Osteoarthritis in a Rat Model

Background: In this study, we investigated the in vitro and in vivo chondrogenic capacity of kartogenin (KGN)–enhanced bone marrow–derived mesenchymal stem cells (BMSCs) for cartilage regeneration. Purpose: To determine (1) whether functionalized nanographene oxide (NGO) can effectively deliver KGN into BMSCs and (2) whether KGN would enhance BMSCs during chondrogenesis in vitro and in vivo in an animal model. Study Design: Controlled laboratory study. Methods: Functionalized NGO with line chain amine-terminated polyethylene glycol (PEG) and branched polyethylenimine (BPEI) were used to synthesize biocompatible NGO-PEG-BPEI (PPG) and for loading hydrophobic KGN molecules noncovalently via π–π stacking and hydrophobic interactions (PPG-KGN). Then, PPG-KGN was used for the intracellular delivery of hydrophobic KGN by simple mixing and co-incubation with BMSCs to acquire KGN-enhanced BMSCs. The chondrogenic efficacy of KGN-enhanced BMSCs was evaluated in vitro. In vivo, osteoarthritis (OA) was induced by anterior cruciate ligament transection in rats. A total of 5 groups were established: normal (OA treated with nothing), phosphate-buffered saline (PBS; intra-articular injection of PBS), PPG-KGN (intra-articular injection of PPG-KGN), BMSCs (intra-articular injection of BMSCs), and BMSCs + PPG-KGN (intra-articular injection of PPG-KGN–preconditioned BMSCs). At 6 and 9 weeks after the surgical induction of OA, the rats received intra-articular injections of PPG-KGN, BMSCs, or KGN-enhanced BMSCs. At 14 weeks after the surgical induction of OA, radiographic and behavioral evaluations as well as histological analysis of the knee joints were performed. Results: The in vitro study showed that PPG could be rapidly uptaken in the first 4 hours after incubation, reaching saturation at 12 hours and accumulating in the lysosome and cytoplasm of BMSCs. Thus, PPG-KGN could enhance the efficiency of the intracellular delivery of KGN, which showed a remarkably high chondrogenic differentiation capacity of BMSCs. When applied to an OA model of cartilage injuries in rats, PPG-KGN–preconditioned BMSCs contributed to protection from joint space narrowing, pathological mineralization, OA development, and OA-induced pain, as well as improved tissue regeneration, as evidenced by radiographic, weightbearing, and histological findings. Conclusion: Our results demonstrate that KGN-enhanced BMSCs showed markedly improved capacities for chondrogenesis and articular cartilage repair. We believe that this work demonstrates that a multifunctional nanoparticle-based drug delivery system could be beneficial for stem cell therapy. Our results present an opportunity to reverse the symptoms and pathophysiology of OA. Clinical Relevance: The intracellular delivery of KGN to produce BMSCs with enhanced chondrogenic potential may offer a new approach for the treatment of OA.

PEGylating poly(p-phenylene vinylene)-based bioimaging nanoprobes

HypothesisConjugated polymer nanoparticles (CNPs) have attracted considerable attention within bioimaging due to their excellent optical properties and biocompatibility. However, unspecific adsorption of proteins hampers their effective use as advanced bioimaging probes. Controlled methodologies made possible tailor-made functional poly(p-phenylene vinylene), enabling one-pot synthesis of CNPs containing functional surface groups. Hence, it should be feasible to PEGylate these CNPs to tune the uptake by cell lines representative for the brain without imparting their optical properties. ExperimentsCNPs consisting of the statistical copolymer 2-(5′-methoxycarbonylpentyloxy)-5-methoxy-1,4-phenylenevinylene and poly(2-methoxy-5-(3′,7′-dimethoxyoctyloxy)-1,4-phenylenevinylene) were fabricated by miniemulsion solvent evaporation technique. Surface carboxylic acid groups were used to covalently attach amine-terminated polyethylene glycol (PEG) of different molecular weights. We investigated the effect of grafting CNPs with PEG chains on their intrinsic optical properties, protein adsorption behavior and uptake by representative brain cell lines. FindingsPEGylation did not affect the optical properties and biocompatibility of our CNPs. Moreover, a significant decrease in protein corona formation and unspecific uptake in central nervous system cell lines, depending on PEG chain length, was observed. This is the first report indicating that PEGylation does not affect the CNPs role as excellent bioimaging tools and can be adapted to tune biological interactions with brain cells.

A novel de-coupling solid polymer electrolyte via semi-interpenetrating network for lithium metal battery

Compared with linear homopolymer and block copolymer electrolytes, network-based solid polymer electrolytes (SPEs) demonstrated much improved lithium dendrite resistance and cell cyclability in lithium metal batteries (LMBs), suggesting that polymer chain architecture plays a pivotal role in SPE design. To further improve the state-of-the-art performance of SPEs, in this work, we report a novel interpenetrating network (IPN) SPE that is comprised of poly (ethylene oxide) and poly (propylene carbonate) (PPC) chains. The synthesis of the SPE is based on the crosslinking of octakis(3-glycidyloxypropyldimethylsiloxy)octasilsesquioxane and amine-terminated polyethylene glycol while incorporating linear PPC with a controlled concentration. The IPN SPEs showed improved ionic conductivity and a nearly threefold increase of lithium ion transference number. The optimized SPE could be stably cycled for over 300 ​h ​at a harsh current density of 1.5 ​mA ​cm−2 in the galvanostatic symmetrical cell plating/stripping experiment. Scanning electron microscopy (SEM) revealed that incorporation of PPC could effectively reduce the uneven lithium deposition while X-ray photoelectron spectroscopy (XPS) was used to confirm the active components that are associated with the stable solid electrolyte interface. Full LMBs fabricated using the IPN SPE, a lithium metal anode and a LiFePO4 cathode delivered high specific capacity of over 160 ​mAh g−1 at 0.1 C and over 95 ​mAh g−1 at 2 ​C with an excellent Coulombic efficiency and lifetime. This work demonstrated a new pathway of SPE molecular design towards high performance SPEs for LMB applications.

Mussel-Inspired Multivalent Linear Polyglycerol Coatings Outperform Monovalent Polyethylene Glycol Coatings in Antifouling Surface Properties.

Biofouling constitutes a major challenge in the application of biosensors and biomedical implants, as well as for (food) packaging and marine equipment. In this work, an antifouling surface coating based on the combination of mussel-inspired dendritic polyglycerol (MI-dPG) and an amine-functionalized block copolymer of linear polyglycerol (lPG-b-OA11, OA = oligo-amine) was developed. The coating was compared to a MI-dPG surface which was postfunctionalized with commercially available amine-terminated polyethylene glycol (HO-PEG-NH2) of similar molecular weight. In the current work, these coatings were compared in their chemical stability, protein fouling characteristics, and cell fouling characteristics. The lPG-b-OA11-functionalized coating showed high chemical stability in both phosphate buffered saline (PBS) and sodium dodecyl sulfate (SDS) solutions and reduced the adhesion of fibrinogen from human plasma with 99% and the adhesion of human serum albumin with 96%, in comparison to the bare titanium dioxide substrate. Furthermore, the proliferation of human umbilical vein endothelial cells (HUVECs) was reduced with 85% when the lPG-b-OA11 system was compared to bare titanium dioxide. Additionally, a reduction of 94% was observed when the lPG-b-OA11 system was compared to tissue culture polystyrene.

Autoxidized Oleic Acid Bifunctional Macro Peroxide Initiators for Free Radical and Condensation Polymerization. Synthesis and Characterization of Multiblock Copolymers

Autoxidation of unsaturated fatty acids gives fatty acid macroperoxide initiators containing two functionalities which can lead to free radical and condensation polymerizations in a single pot. The oleic acid macroperoxide initiator obtained by ecofriendly autoxidation (Pole4m) was used in both the free radical polymerization of styrene and the condensation polymerization with amine-terminated polyethylene glycol (PEGNH2) to obtain triblock branched graft copolymers. The narrow molar masses of the poly oleic acid-g-styrene (PoleS) and poly oleic acid-g-styrene-g-PEG (PoSG) graft copolymers were successfully obtained. The inclusion of oleic acid decreased the glass transition temperature of the polystyrene segment because of the plasticizing effect of oleic acid. In addition, a mechanical property of the copolymer was improved when compared with the pure PS. Structural characterization, morphology of the fracture surface, micelle formation, thermal analysis and molar masses of the obtained products were also evaluated.

Defect-free surface modification methods for solubility-tunable carbon nanotubes

Although carbon nanotubes (CNTs) have outstanding physical properties, there are still challenging issues such as poor dispersibility and miscibility between organic polymers and CNTs for polymer nanocomposites. Chemical modifications (e.g., strong acid based oxidation, carboxylation, etc.) can improve dispersion properties and compatibility, but such surface modification methods often lead to damage to the pristine CNT structure and also deteriorate the mechanical properties of CNTs. Here we demonstrate a simple, defect-free and scalable method for well-dispersed CNTs in common organic solvents, using dopamine and amine-terminated polyethylene glycol derivatives. This method makes it possible to prepare solubility-tunable CNTs without any severe structural deformation. As-modified CNTs were successfully characterized by thermal gravimetric analysis (TGA), Fourier-transformed infrared spectroscope (FT-IR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and transmission electron microscope (TEM). The surface modified-CNTs were well-dispersed in polar and/or non-polar common solvents. The well-dispersed CNTs can be used in a nanofiller in commercial polymers such as thermoplastic polyurethane (TPU) polymer. The CNT/TPU composite showed improved tensile strength without sacrificing elongation at break relative to those of pristine TPU.

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles.

Nanomedicine is an emerging form of therapy that harnesses the unique properties of particles that are nanometers in scale for biomedical application. Improving drug delivery to maximize therapeutic outcomes and to reduce drug-associated side effects are some of the cornerstones of present-day nanomedicine. Nanoparticles in particular have found a wide application in cancer treatment. Nanoparticles that offer a high degree of flexibility in design, application, and production based on the tumor microenvironment are projected to be more effective with rapid translation into clinical practice. The polymeric micellar nano-carrier is a popular choice for drug delivery applications. In this article, we describe a simple and effective protocol for synthesizing drug-loaded, disulfide cross-linked micelles based on the self-assembly of a well-defined amphiphilic linear-dendritic copolymer (telodendrimer, TD). TD is composed of polyethylene glycol (PEG) as the hydrophilic segment and a thiolated cholic acid cluster as the core-forming hydrophobic moiety attached stepwise to an amine-terminated PEG using solution-based peptide chemistry. Chemotherapy drugs, such as paclitaxel (PTX), can be loaded using a standard solvent evaporation method. The O2-mediated oxidation was previously utilized to form intra-micellar disulfide cross-links from free thiol groups on the TDs. However, the reaction was slow and not feasible for large-scale production. Recently, an H2O2-mediated oxidation method was explored as a more feasible and efficient approach, and it was 96 times faster than the previously reported method. Using this approach, 50 g of PTX-loaded, disulfide cross-linked nanoparticles have been successfully produced with narrow particle size distribution and high drug loading efficiency. The stability of the resulting micelle solution is analyzed using disrupting conditions such as co-incubation with a detergent, sodium dodecyl sulfate, with or without a reducing agent. The drug-loaded, disulfide cross-linked micelles demonstrated less hemolytic activity when compared to their non-cross-linked counterparts.

Improvement of the Thermal Stability of TEMPO‐Oxidized Cellulose Nanofibrils by Heat‐Induced Conversion of Ionic Bonds to Amide Bonds

Improving thermal stability of TEMPO-oxidized cellulose nanofibrils (TOCNs) is a major challenge for the development and preparation of new nanocomposites. However, thermal degradation of TOCNs occurs at 220 °C. The present study reports a simple way to improve thermal stability of TOCNs by the heat-induced conversion of ionic bonds to amide bonds. Coupling amine-terminated polyethylene glycol to the TOCNs is performed through ionic bond formation. Films are produced from the dispersions by the casting method. Infrared spectroscopy and thermogravimetric analysis confirm conversion of ionic bonds to amide bonds for the modified TOCN samples after heating. As a result, improvement of TOCNs' thermal stability by up to 90 °C is successfully achieved.

A multifunctional amphiphilic polymer as a platform for surface-functionalizing metallic and other inorganic nanostructures.

We designed a new set of polymer ligands that combine multiple metal-coordinating groups and short polyethylene glycol (PEG) moieties in the same structure. The ligand design relies on the controlled grafting of a large number of amine-terminated histamines and PEG short chains onto a poly(isobutylene-alt-maleic anhydride) backbone, via a one-step nucleophilic addition reaction. This addition reaction is highly efficient, can be carried out in organic media and does not require additional reagents. We show that when imidazole groups are used the resulting polymer ligand can strongly ligate onto metal nanostructures such as nanoparticles (NPs) and nanorods (NRs) made of gold cores. The resulting polymer-coated NPs and NRs exhibit good colloidal stability to pH changes and added electrolytes. This constitutes a departure from the use of thiol-based ligands to coordinate on Au surfaces. The present chemical approach also opens up additional opportunities for designing hydrophilic and reactive platforms where the polymer coating can be adjusted to various metal and metal oxide surfaces by simply modifying or combining the addition reaction with other metal coordinating groups. These could include iron oxide NPs and semiconductor QDs. These polymer-capped NPs and NRs can be used to develop biologically-active platforms with potential use for drug delivery and sensing.

Comparison of mechanical reinforcement effects of surface-modified cellulose nanofibrils and carbon nanotubes in PLLA composites

Cellulose nanofibrils were prepared using 2,2,6,6-tetramethylpiperidiniyl-1-oxyl (TEMPO)-mediated oxidation of wood cellulose, and the surfaces of the resulting TEMPO-oxidized cellulose nanofibrils (TOCNs) were grafted with amine-terminated polyethylene glycol (PEG) chains via ionic bonds. PEG-TOCN/PLLA composite films were prepared by casting mixtures of various ratios of PEG-TOCN/chloroform dispersion and PLLA/chloroform solution. The mechanical reinforcement properties of PEG-TOCNs prepared using PEG-NH2 of two different PEG chain lengths were evaluated using tensile tests and compared against those of PEG-grafted single-walled carbon nanotubes (PEG-SWCNT). PEG-TOCNs were individually dispersed in the PLLA matrix so that the Young’s modulus increased with PEG-TOCN content, following theoretically predicted values. In contrast, the PEG-SWCNT formed aggregates in the PLLA matrix, probably owing to heterogeneous distribution of carboxyl groups. As a result, PEG-TOCN/PLLA composites showed superior properties to those of PEG-SWCNT/PLLA composites in terms of optical transparency, strength, and toughness.

A facile synthesis of polyaniline/polyethylene glycol/polyaniline terpolymers: preparation of electrospun conducting nanofibers by blending of the terpolymers with polycaprolactone

The water-soluble terpolymers were synthesized in two steps, containing esterification of polyethylene glycol (PEG) and 4-amino benzoic acid without protection of its amino group, then copolymerization of aniline from both end of amine-terminated PEG via an interfacial polymerization method. The chemical structure of triblock copolymers was determined by FTIR and 1HNMR. The thermal behavior, morphology and electroactivity of terpolymers were also investigated by thermogravimetric analysis, field emission microscope (FESEM) and cyclic voltammetry (CV), respectively. Uniform nanofibers consisting of blends of (PANI)n-b-PEG-b-(PANI)n terpolymers and polycaprolactone (PCL) were prepared using electrospinning technique. The FESEM was also used to investigate the electrospun nanofibers produced from different molecular weight of PANI/PEG/PANI terpolymers and PCL (30/70). The CV measurements of blends confirmed the preparation of electroactive nanofibers. The presence of terpolymers enhanced the spinnability of solution and significantly reduced the bead formation. This novel system opens up new and interesting opportunities for applications such as electroactive scaffold for tissue engineering.

Functionalized Graphene Oxide in Enzyme Engineering: A Selective Modulator for Enzyme Activity and Thermostability

The understanding of interactions between nanomaterials and biomolecules is of fundamental importance to the area of nanobiotechnology. Graphene and its derivative, graphene oxide (GO), are two-dimensional (2-D) nanomaterials with interesting physical and chemical properties and have been widely explored in various directions of biomedicine in recent years. However, how functionalized GO interacts with bioactive proteins such as enzymes and its potential in enzyme engineering have been rarely explored. In this study, we carefully investigated the interactions between serine proteases and GO functionalized with different amine-terminated polyethylene glycol (PEG). Three well-characterized serine proteases (trypsin, chymotrypsin, and proteinase K) with important biomedical and industrial applications were analyzed. It is found that these PEGylated GOs could selectively improve trypsin activity and thermostability (60-70% retained activity at 80 °C), while exhibiting barely any effect on chymotrypsin or proteinase K. Detailed investigation illustrates that the PEGylated GO-induced acceleration is substrate-dependent, affecting only phosphorylated protein substrates, and that at least up to 43-fold increase could be achieved depending on the substrate concentration. This unique phenomenon, interestingly, is found to be attributed to both the terminal amino groups on polymer coatings and the 2-D structure of GO. Moreover, an enzyme-based bioassay system is further demonstrated utilizing our GO-based enzyme modulator in a proof-of-concept experiment. To our best knowledge, this work is the first success of using functionalized GO as an efficient enzyme positive modulator with great selectivity, exhibiting a novel potential of GO, when appropriately functionalized, in enzyme engineering as well as enzyme-based biosensing and detection.

Dual-modality photothermal optical coherence tomography and magnetic-resonance imaging of carbon nanotubes

We demonstrate polyethylene-glycol-coated single-walled carbon nanotubes (CNTs) as contrast agents for both photothermal optical coherence tomography (OCT) and magnetic-resonance imaging (MRI). Photothermal OCT was accomplished with a spectral domain OCT system with an amplitude-modulated 750 nm pump beam using 10 mW of power, and T(2) MRI was achieved with a 4.7 T animal system. Photothermal OCT and T(2) MRI achieved sensitivities of nanomolar concentrations to CNTs dispersed in amine-terminated polyethylene glycol, thus establishing the potential for dual-modality molecular imaging with CNTs.

Doxorubicin loaded iron oxide nanoparticles overcome multidrug resistance in cancer in vitro

Multidrug resistance (MDR) is characterized by the overexpression of ATP-binding cassette (ABC) transporters that actively pump a broad class of hydrophobic chemotherapeutic drugs out of cancer cells. MDR is a major mechanism of treatment resistance in a variety of human tumors, and clinically applicable strategies to circumvent MDR remain to be characterized. Here we describe the fabrication and characterization of a drug-loaded iron oxide nanoparticle designed to circumvent MDR. Doxorubicin (DOX), an anthracycline antibiotic commonly used in cancer chemotherapy and substrate for ABC-mediated drug efflux, was covalently bound to polyethylenimine via a pH sensitive hydrazone linkage and conjugated to an iron oxide nanoparticle coated with amine terminated polyethylene glycol. Drug loading, physiochemical properties and pH lability of the DOX-hydrazone linkage were evaluated in vitro. Nanoparticle uptake, retention, and dose-dependent effects on viability were compared in wild-type and DOX-resistant ABC transporter over-expressing rat glioma C6 cells. We found that DOX release from nanoparticles was greatest at acidic pH, indicative of cleavage of the hydrazone linkage. DOX-conjugated nanoparticles were readily taken up by wild-type and drug-resistant cells. In contrast to free drug, DOX-conjugated nanoparticles persisted in drug-resistant cells, indicating that they were not subject to drug efflux. Greater retention of DOX-conjugated nanoparticles was accompanied by reduction of viability relative to cells treated with free drug. Our results suggest that DOX-conjugated nanoparticles could improve the efficacy of chemotherapy by circumventing MDR.

Amplification free detection of Herpes Simplex Virus DNA

Amplification-free detection of nucleic acids in complex biological samples is an important technology for clinical diagnostics, especially in the case where the detection is quantitative and highly sensitive. Here we present the detection of a synthetic DNA sequence from Herpes Simplex Virus-1 within swine cerebrospinal fluid (CSF), using a sandwich-like, magnetic nanoparticle pull-down assay. Magnetic nanoparticles and fluorescent polystyrene nanoparticles were both modified with DNA probes, able to hybridise either end of the target DNA, forming the sandwich-like complex which can be captured magnetically and detected by fluorescence. The concentration of the target DNA was determined by counting individual and aggregated fluorescent nanoparticles on a planar glass surface within a fluidic chamber. DNA probe coupling for both nanoparticles was optimized. Polystyrene reporter nanoparticles that had been modified with amine terminated DNA probes were also treated with amine terminated polyethylene glycol, in order to reduce non-specific aggregation and target independent adhesion to the magnetic particles. This way, a limit of detection for the target DNA of 0.8 pM and 1 pM could be achieved for hybridisation buffer and CSF respectively, corresponding to 0.072 and 0.090 femtomoles of target DNA, in a volume of 0.090 mL.

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.