Encapsulation and Delivery of Neutrophic Proteins and Hydrophobic Agents Using PMOXA-PDMS-PMOXA Triblock Polymersomes.

Polymersomes are attractive nanocarriers for hydrophilic and lipophilic drugs; they are more stable than liposomes, tunable, and relatively easy to prepare. The copolymer composition and molar mass are critical features that determine the physicochemical properties of the polymersomes including the rate of drug release. We used the triblock-copolymer, poly(2-methyl-2-oxazoline)--poly-(dimethysiloxane)--poly(2-methyl-2-oxazoline) (PMOXA-PDMS-PMOXA), to form amphipathic polymersomes capable of loading proteins and small hydrophobic agents.

Quantum dot agglomerates in biological media and their characterization by asymmetrical flow field-flow fractionation.

The molecular composition of the biological environment of nanoparticles influences their physical properties and changes their pristine physicochemical identity. In order to understand, or predict, the interactions of cells with specific nanoparticles, it is critical to know their size, shape, and agglomeration state not only in their nascent state but also in biological media. Here, we use asymmetrical flow field-flow fractionation (AF4) with on-line multiangle light scattering (MALS), dynamic light scattering (DLS) and UV-Visible absorption detections to determine the relative concentration of isolated nanoparticles and agglomerates in the case of three types of semi-conductor quantum dots (QDs) dispersed in Dulbecco's Modified Eagle Media (DMEM) containing 10% of fetal bovine serum (DMEM-FBS).

Quantum dots for imaging neural cells in vitro and in vivo.

Quantum dots (QDs) have been used for optical imaging of neural cells in vitro and in vivo. This chapter lists the basic materials, instrumentation and step-by-step procedures to image live microglia cells and to show the functional and biochemical changes in microglia exposed to QDs. Details are also provided for the real-time imaging of cerebral ischemic lesions in animals and for the assessment of lesion reduction after therapeutic interventions.

"Click" dendrimers as anti-inflammatory agents: with insights into their binding from molecular modeling studies.

These studies explore the relationship between the inhibitory actions of low generation dendrimers in stimulated microglia and dendrimer-enzyme interactions using in silico molecular modeling. Low generation (DG0 and DG1) dendrimers with acetylene and hydroxyl terminal groups were tested for their anti-inflammatory activity in microglia stimulated by lipopolysaccharides (LPS), and the results were compared with those from the established anti-inflammatory agents, ibuprofen and celecoxib. We hypothesized that hydroxyl terminal groups of DG0 and DG1 dendrimers could interact with the active sites of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) enzymes due to their small size and favorable electrochemical properties.

Wound-healing with mechanically robust and biodegradable hydrogel fibers loaded with silver nanoparticles.

The objective of this study is to provide a novel synthetic approach for the manufacture of wound-healing materials using covalently cross-linked alginate fibers loaded with silver nanoparticles. Alginate fibers are prepared by wet-spinning in a CaCl(2) precipitation bath. Using this same approach, calcium cross-links in alginate fibers are replaced by chemical cross-links that involve hydroxyl groups for subsequent cross-linking by glutaraldehyde.

Short ligands affect modes of QD uptake and elimination in human cells.

In order to better understand nanoparticle uptake and elimination mechanisms, we designed a controlled set of small, highly fluorescent quantum dots (QDs) with nearly identical hydrodynamic size (8-10 nm) but with varied short ligand surface functionalization. The properties of functionalized QDs and their modes of uptake and elimination were investigated systematically by asymmetrical flow field-flow fractionation (AF4), confocal fluorescence microscopy, flow cytometry (FACS), and flame atomic absorption (FAA). Using specific inhibitors of cellular uptake and elimination machinery in human embryonic kidney cells (Hek 293) and human hepatocellular carcinoma cells (Hep G2), we showed that QDs of the same size but with different surface properties were predominantly taken up through lipid raft-mediated endocytosis, however, to significantly different extents.

Mechanisms of cellular adaptation to quantum dots--the role of glutathione and transcription factor EB.

Cellular adaptation is the dynamic response of a cell to adverse changes in its intra/extra cellular environment. The aims of this study were to investigate the role of: (i) the glutathione antioxidant system, and (ii) the transcription factor EB (TFEB), a newly revealed master regulator of lysosome biogenesis, in cellular adaptation to nanoparticle-induced oxidative stress. Intracellular concentrations of glutathione species and activation of TFEB were assessed in rat pheochromocytoma (PC12) cells following treatment with uncapped CdTe quantum dots (QDs), using biochemical, live cell fluorescence and immunocytochemical techniques.

Probing and preventing quantum dot-induced cytotoxicity with multimodal alpha-lipoic acid in multiple dimensions of the peripheral nervous system.

Aim: Toxicity of nanoparticles developed for biomedical applications is extensively debated as no uniform guidelines are available for studying nanomaterial safety, resulting in conflicting data obtained from different cell types. This study demonstrates the varied toxicity of a selected type of nanoparticle, cadmium telluride quantum dots (QDs), in three increasingly complex cell models of the peripheral nervous system.

Materials & Methods: QD-induced cytotoxicity was assessed via cell viability assays and biomarkers of subcellular damage in PC12 cells and mixed primary dispersed dorsal root ganglia (DRG) cultures.