A universal approach to ultrasmall magneto-fluorescent nanohybrids.

Seeded emulsion polymerization is a powerful universal method to produce ultrasmall multifunctional magnetic nanohybrids. In a two-step procedure, iron oxide nanocrystals were initially encapsulated in a polystyrene (PS) shell and subsequently used as beads for a controlled assembly of elongated quantum dots/quantum rods (QDQRs). The synthesis of a continuous PS shell allows the whole construct to be fixed and the composition of the nanohybrid to be tuned. The fluorescence of the QDQRs and magnetism of iron oxide were perfectly preserved, as confirmed by single-particle investigation, fluorescence decay measurements, and relaxometry. Bio-functionalization of the hybrids was straightforward, involving copolymerization of appropriate affinity ligands as shown by immunoblot analysis. Additionally, the universality of this method was shown by the embedment of a broad scale of NPs.

Polymer-assisted self-assembly of superparamagnetic iron oxide nanoparticles into well-defined clusters: controlling the collective magnetic properties.

The combination of superstructure-forming amphiphilic block copolymers and superparamagnetic iron oxide nanoparticles produces new nano/microcomposites with unique size-dependent properties. Herein, we demonstrate the controlled clustering of superparamagnetic iron oxide nanoparticles (SPIOs) ranging from discretely encapsulated SPIOs to giant clusters, containing hundreds or even more particles, using an amphiphilic polyisoprene-block-poly(ethylene glycol) diblock copolymer. Within these clusters, the SPIOs interact with each other and show new collective properties, neither obtainable with singly encapsulated nor with the bulk material. We observed cluster-size-dependent magnetic properties, influencing the blocking temperature, the magnetoviscosity of the liquid suspension, and the r2 relaxivity for magnetic iron oxide nanoparticles. The clustering methodology can be expanded also to other nanoparticle materials [CdSe/CdS/ZnS core/shell/shell quantum dots (QDs), CdSe/CdS quantum dots/quantum rods (QDQRs), gold nanoparticles, and mixtures thereof].

Glycoconjugated amphiphilic polymers via click-chemistry for the encapsulation of quantum dots.

Herein, we present a strategy for the glycoconjugation of nanoparticles (NPs), with a special focus on fluorescent quantum dots (QDs), recently described by us as "preassembly" approach. Therein, prior to the encapsulation of diverse nanoparticles by an amphiphilic poly(isoprene)-b-poly(ethylene glycol) diblock copolymer (PI-b-PEG), the terminal PEG appendage was modified by covalently attaching a carbohydrate moiety using Huisgen-type click-chemistry. Successful functionalization was proven by NMR spectroscopy. The terminally glycoconjugated polymers were subsequently used for the encapsulation of QDs in a phase transfer process, which fully preserved fluorescence properties. Binding of these nanoconstructs to the lectin Concanavalin A (Con A) was studied via surface plasmon resonance (SPR). Depending on the carbohydrate moiety, namely, D-manno-heptulose, D-glucose, D-galactose, 2-deoxy-2-{[methylamino)carbonyl]amino}-D-glucopyranose ("des(nitroso)-streptozotocin"), or D-maltose, the glycoconjugated QDs showed enhanced affinity constants due to multivalent binding effects. None of the constructs showed toxicity from 0.001 to 1 µM (particle concentration) using standard WST and LDH assays on A549 cells.

Amphiphilic, cross-linkable diblock copolymers for multifunctionalized nanoparticles as biological probes.

Nanoparticles (NPs) play an increasingly important role in biological labeling and imaging applications. However, preserving their useful properties in an aqueous biological environment remains challenging, even more as NPs therein have to be long-time stable, biocompatible and nontoxic. For in vivo applications, size control is crucial in order to route excretion pathways, e.g. renal clearance vs. hepato-biliary accumulation. Equally necessary, cellular and tissue specific targeting demands suitable linker chemistry for surface functionalization with affinity molecules, like peptides, proteins, carbohydrates and nucleotides. Herein, we report a three stage encapsulation process for NPs comprised of (1) a partial ligand exchange by a multidentate polyolefinic amine ligand, PI-N3, (2) micellar encapsulation with a precisely tuned amphiphilic diblock PI-b-PEG copolymer, in which the PI chains intercalate to the PI-N3 prepolymer and (3) radical cross-linking of the adjacent alkenyl bonds. As a result, water-soluble NPs were obtained, which virtually maintained their primal physical properties and were exceptionally stable in biological media. PEG-terminal functionalization of the diblock PI-b-PEG copolymer with numerous functional groups was mostly straightforward by chain termination of the living anionic polymerization (LAP) with the respective reagents. More complex affinity ligands, e.g. carbohydrates or biotin, were introduced in a two-step process, prior to micellar encapsulation. Advantageously, this pre-assembly approach opens up rapid access to precisely tuned multifunctional NPs, just by using mixtures of diverse functional PI-b-PEG polymers in a combinatorial manner. All constructs showed no toxicity from 0.001 to 1 µM (particle concentration) in standard WST and LDH assays on A549 cells, as well as only marginal unspecific cellular uptake, even in serum-free medium.

In situ functionalization and PEO coating of iron oxide nanocrystals using seeded emulsion polymerization.

Herein we demonstrate that seeded emulsion polymerization is a powerful tool to produce multiply functionalized PEO coated iron oxide nanocrystals. Advantageously, by simple addition of functional surfactants, functional monomers, or functional polymerizable linkers-solely or in combinations thereof-during the seeded emulsion polymerization process, a broad range of in situ functionalized polymer-coated iron oxide nanocrystals were obtained. This was demonstrated by purposeful modulation of the zeta potential of encapsulated iron oxide nanocrystals and conjugation of a dyestuff. Successful functionalization was unequivocally proven by TXRF. Furthermore, the spatial position of the functional groups can be controlled by choosing the appropriate spacers. In conclusion, this methodology is highly amenable for combinatorial strategies and will spur rapid expedited synthesis and purposeful optimization of a broad scope of nanocrystals.

Effective medical education: insights from the Cochrane Library.

UNLABELLED: In 2006, the Accreditation Council for Continuing Medical Education highlighted the need for linking educational activities to changes in competence, performance, or patient outcomes. Hence, educational providers increasingly need to know what strategies are effective. The Cochrane Library is widely regarded as the best source of credible evidence concerning health care. The authors searched the Cochrane Database of Systematic Reviews (issue 4 for 2006) using the search terms "continuing medical education," "medical education," and "continuing education." They conducted a second complementary search of this database by review group (Effective Practice and Organization of Care). Finally, the authors examined the references of recent review articles for Cochrane reviews and found 9 relevant reviews. The most effective educational methods were the most interactive. Combined didactic presentations and workshops were more effective than traditional didactic presentations alone. Medical education was more effective when more than 1 intervention occurred, especially if these interventions occurred over an extended period. Targeted education should focus on changing a behavior that is simple, because effect size is inversely proportional to the complexity of the behavior. In the era of evidence-based medicine, interventions-including educational ones-should reflect the best available evidence. Cochrane reviews of randomized controlled trials of educational methods provide important guidance that often challenges traditional didactic approaches. Integrating the findings from the Cochrane reviews may allow continuing medical education to be more successful in bringing about changes to healthcare providers' behavior. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to explain the scientific evidence concerning the effectiveness of various techniques used for continuing medical education, state the relative value of such techniques as traditional didactic lectures, conferences led by local opinion leaders, interactive workshops, and educational outreach visits, and identify the value and limitations of teaching critical appraisal skills.