Combined ATRP and 'click' chemistry for designing stable tumor-targeting superparamagnetic iron oxide nanoparticles

Important issues in the design of superparamagnetic iron oxide nanoparticles (SPIONs) for cancer diagnosis include stability under physiological conditions and specificity in targeting the cancer cells. In the present study, atom transfer radical polymerization (ATRP) was used to graft SPIONs with poly(glycidyl methacrylate-co-poly(ethylene glycol) methyl ether methacrylate) (SPIONs-P(GMA-co-PEGMA)). The PEGMA in the copolymer chain confers high stability to the nanoparticles in aqueous medium, and prevents recognition by macrophages with the aim of prolonging their in vivo circulation time. The GMA groups were used for conjugating the cancer targeting ligand, folic acid (FA), via 'click' chemistry. Using this method, the amount of FA conjugated to the nanoparticles (SPIONs-P(GMA-co-PEGMA)-FA) can be readily controlled. The specificity of cellular uptake of the nanoparticles by three different cell lines was investigated. The cellular iron uptake by KB cells (human epidermoid carcinoma) after 24 h of incubation is about thirteen and five times higher than those by 3T3 fibroblasts and macrophages, respectively. No significant cytotoxicity was observed with these three types of cells. The high targeting efficiency and biocompatibility of these nanoparticles are promising features for in vivo specific targeting and detection of tumor cells which overexpress the folate receptor.     

Reaction pathways of Sc+ (3D, 1D) and Fe+ (6D, 4F) with acetone in the gas phase: metal ion oxidation and acetone deethanization

The reactions of Sc⁺ (³D, ¹D) and Fe⁺ (⁶D, ⁴ F) with acetone have been investigated in both high‐ and low‐spin states using density functional theory. Our calculations have indicated that oxidation of Sc⁺ by acetone can take place by (1) metal‐mediated H migration, (2) direct methyl‐H shift and/or (3) C = O insertion. The most energetically favorable pathway is metal‐mediated H migration followed by intramolecular ScO⁺ rotation and dissociation. For the deethanization of acetone mediated by Fe⁺, the reaction occurs on either the quartet or sextet surfaces through five elementary steps, i.e. encounter complexation, C–C bond activation, methyl migration, C–C coupling and non‐reactive dissociation. The rate‐determining step along the quartet‐state potential‐energy surface (PES) is similar to that in the case of Ni⁺ (² F, 3d⁹), namely the methyl‐migration step. For the sextet‐state PES, however, the energy barrier for methyl migration is lower than that for C–C bond activation, and the rate‐determining step is C–C coupling. In general, the low‐spin‐state pathways are lower in energy than the high‐spin‐state pathways; therefore, the reaction pathways for the oxidation of Sc⁺ and the Fe⁺‐mediated deethanization of acetone mostly involve the low‐spin states. Copyright © 2012 John Wiley & Sons, Ltd.     

Advancements and current challenges in the sustainable downstream processing of bacterial polyhydroxyalkanoates

Diminishing sources of synthetic plastics and their unsustainable production processes have increased the demand for alternative biodegradable and sustainable polymers. Bacterial biopolymer-producing factories can carry out large-scale production of such alternatives using improved fermentation techniques, such as fed-batch and pulsed feeding of inducers, that can increase bacterial biopolymer accumulation. However, the successive downstream processing (DSP) techniques still pose challenges in making the production process both economically and environmentally sustainable. These challenges are mostly associated with biomass pre-treatment, the use of solvents, and the embedded parameters of the DSP techniques. Conventional halogenated/chlorinated solvents can be substituted with green solvents to yield PHAs of high purity (98%) for high-end applications and to establish a sustainable circular economy. As an economically and environmentally sustainable approach, the use of recycled waste as a substrate and greener extraction solvents for bacterial biopolymer production should be further explored for the efficient replacement of synthetic plastic production.     

Synthesis and characterization of random and block copolymers with pendant rhenium diimine complexes by controlled radical polymerization

We report the polymerization of rhenium‐containing methacrylates by atom transfer radical polymerization. The structure of the monomer was confirmed by X‐ray crystallography, which showed the bulkiness of the metal‐complex moiety. The rhenium complexes were polymerized in the presence of copper(I) bromide, 1,1,4,7,7‐pentamethyldiethylenetriamine, and methyl 2‐bromopropionate. They were copolymerized with methyl methacrylate in different monomer ratios. An ABA triblock copolymer was also synthesized with poly(methyl methacrylate) as the macroinitiator. When 2,2′‐bipyridine was used as the ligand for the copper catalyst in the polymerizations, it underwent a ligand exchange process with the iminopyridine ligand in the monomer. The neutral rhenium complex in the homopolymers and copolymers could be converted into ionic forms by the replacement of the chloride with an imidazole ligand, and the solubility of the resulting ionic polymers was greatly enhanced. The photosensitizing properties of the doped and undoped polymer films were investigated by the measurement of the photocurrent response under an externally applied electric field. The photoconductivities of the polymers were approximately 10^?12–10^?13 Ω^?1 cm^?1. The experimental quantum efficiencies were simulated with Onsager's theory, and they showed that the initial quantum yield and thermalization distance were 10^?3 and 1.7 nm, respectively. Transmission electron microscopy showed that the rhenium complexes aggregated to form domains with dimensions of approximately 20–30 nm. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1292–1308, 2005     

A high-throughput microfluidic biochip to quantify bacterial adhesion to single host cells by real-time PCR assay

A high-throughput microfluidic poly-(dimethylsiloxane) biochip was developed to quantify bacterial adhesion to single host cells by real-time PCR assay. The biochip is simply structured with a two-dimensional array of 900 micro-wells, one inlet, and one outlet micro-channels. Isolation of single infected host cells into the individual micro-wells of the biochip was achieved by one-step vacuum-driven microfluidics. The adhered bacterial cells were then quantified by direct on-chip real-time PCR assay with single-bacterium-detection sensitivity. The performance of this microfluidic platform was demonstrated through profiling of the association of a common bacterial pathogen, Pseudomonas aeruginosa, to single host human lung epithelial A549 cells, revealing an adherence distribution that has not been previously reported. This microfluidic platform offers a simple and effective tool for biologists to analyze pathogen–host interaction at the single-cell level without the necessities of fluorescence labeling. The chip can similarly be used for other PCR-based applications requiring single-cell analysis.     

Determination of closantel and rafoxanide in animal tissues by online anionic mixed-mode solid-phase extraction followed by isotope dilution liquid chromatography tandem mass spectrometry

A rapid and high-throughput isotope dilution LC-MS/MS method with online sample pre-concentration and clean-up using anionic mixed-mode SPE was described for the determination of closantel and rafoxanide in edible bovine and ovine tissues. Tissue samples were extracted with acetonitrile and acetone mixture (60:40, v/v). Sample pre-concentration, clean-up and analysis were completed simultaneously with the online MAX SPE LC-MS/MS system. Closantel-(13) C(6) and rafoxanide-(13) C(6) were used as the internal standards to improve the precision of the method. The method was validated with edible ovine and bovine tissues (muscle, kidney and liver) fortified at three different levels. The accuracy and RSD were 86-106% and ≤14%, respectively. This high-throughput method was suitable for routine quantitative analysis of closantel and rafoxanide in food safety surveillance samples.     

Iron cross-linked carboxymethyl cellulose—gelatin complex coacervate beads for sustained drug delivery

The formation and smooth recovery of ibuprofen encapsulated in microcapsules using gelatin and carboxymethyl cellulose (CMC) complex coacervation without glutaraldehyde were the objectives of this investigation. The microcapsules were recovered as ionically cross-linked beads using aqueous ferric chloride in 50 vol.% of 2-propanol. A physical mixture of CMC/gelatin (FP1) and CMC alone (FP2) beads was also prepared for comparison. The drug-entrapment efficiency of complex coacervate beads (FP3-FP5) was dependent on the drug-to-polymer ratio and was in the range of 86–92 mass %. Beads prepared with the highest ratio of the drug (FP5) exhibited the lowest entrapment. FP1 and FP2 beads exhibited an entrapment efficiency of 98.5 mass % and 91.3 mass %, respectively. Infrared spectroscopy (FTIR) revealed different functional groups in complex coacervate, physical mixture and FP2 beads. Optical and scanning electron microscopy revealed the distinct appearance and surface morphology of the various beads. The stable and crystalline nature of ibuprofen in the beads was confirmed by FTIR and differential scanning calorimetry (DSC), respectively. Ibuprofen release from FP1 and FP2 beads was very slow and unsuitable for oral delivery. The bead prepared by complex coacervation (FP5) showed a better release profile over 48 h and could be developed as a sustained drug delivery system.