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.

Caspase-1 activity in microglia stimulated by pro-inflammagen nanocrystals.

Although caspase-1 is a key participant in inflammation, there is no sensitive assay to measure its enzymatic activity in real time in cells or animals. Here we describe a nanosensor for caspase-1 ratiometric measurements, consisting of a rhodamine-labeled, caspase-1 cleavable peptide linked to quantum dots (QDs). Microglia cells were stimulated by lipopolysaccharide (LPS) and by hybrid nanoparticles LPS-QDs.

MicroRNA-21* regulates the prosurvival effect of GM-CSF on human eosinophils.

Eosinophils are the principal effector cells of allergic inflammation, and hematopoietic cytokine granulocyte macrophage colony-stimulating factor (GM-CSF) is the primary cytokine that activates and prolongs the survival of eosinophils in local inflammatory sites by mediating anti-apoptotic activity in allergic inflammation. To investigate the immunopathological role of microRNA (miRNA) in allergic inflammation, we elucidated the regulatory mechanisms of miRNA on the GM-CSF-mediated in vitro survival in eosinophils. Eosinophils were purified from fresh human peripheral blood buffy coat fraction obtained from adult volunteer using microbead magnetic cell sorting.

Activation of eosinophils interacting with dermal fibroblasts by pruritogenic cytokine IL-31 and alarmin IL-33: implications in atopic dermatitis.

Background: IL-31 is a pruritogenic cytokine, and IL-33 is an alarmin for damaging inflammation. They together relate to the pathogenesis of atopic dermatitis (AD). Eosinophil infiltration into the inner dermal compartment is a predominant pathological feature of AD.

Tailoring the efficacy of nimodipine drug delivery using nanocarriers based on A2B miktoarm star polymers.

We report a nanocarrier based on A(2)B type miktoarm polymers (A=polyethylene glycol (PEG); B=polycaprolactone (PCL)) for nimodipine (NIM), a hydrophobic drug with very poor aqueous solubility that is commonly prescribed for the prevention and treatment of delayed ischemic neurological disorders. The A(2)B star polymers were constructed on a core with orthogonal functionalities that facilitated the performance of "click" chemistry followed by ring-opening polymerization. These star polymers assemble into spherical micelles into which NIM can be easily loaded by the co-solvent evaporation method.

Lipopolysaccharide-QD micelles induce marked induction of TLR2 and lipid droplet accumulation in olfactory bulb microglia.

The intranasal entry of biological and artificial nanoparticles can induce inflammatory responses both locally and more widely in surrounding tissues. The aim of this study was to assess the microglia activation induced by nanoparticles with different surfaces in (i) a transgenic mouse (Toll-like receptor (TLR)-2-luciferase (Luc) reporter) which allowed the biophotonic imaging of microglial activation/innate immune response after intranasal delivery of nanoparticles and (ii) in microglial dispersed cells in vitro. Cadmium selenide nanoparticles (quantum dots, QD), surface-exchanged with lipopolysaccharide (LPS) to form micelles, were tested to assess microglia activation and lipid droplet formation in both model systems.

Minocycline block copolymer micelles and their anti-inflammatory effects on microglia.

MH, a semisynthetic tetracycline antibiotic with promising neuroprotective properties, was encapsulated into PIC micelles of CMD-PEG as a potential new formulation of MH for the treatment of neuroinflammatory diseases. PIC micelles were prepared by mixing solutions of a Ca(2+)/MH chelate and CMD-PEG copolymer in a Tris-HCl buffer. Light scattering and (1)H NMR studies confirmed that Ca(2+)/MH/CMD-PEG core-corona micelles form at charge neutrality having a hydrodynamic radius approximately 100 nm and incorporating approximately 50 wt.

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.

Quantum dot-induced epigenetic and genotoxic changes in human breast cancer cells.

The staggering array of nanotechnological products, found in our environment and those applicable in medicine, has stimulated a growing interest in examining their long-term impact on genetic and epigenetic processes. We examined here the epigenomic and genotoxic response to cadmium telluride quantum dots (QDs) in human breast carcinoma cells. QD treatment induced global hypoacetylation implying a global epigenomic response.

Quantum dot-induced cell death involves Fas upregulation and lipid peroxidation in human neuroblastoma cells.

Background: Neuroblastoma, a frequently occurring solid tumour in children, remains a therapeutic challenge as existing imaging tools are inadequate for proper and accurate diagnosis, resulting in treatment failures. Nanoparticles have recently been introduced to the field of cancer research and promise remarkable improvements in diagnostics, targeting and drug delivery. Among these nanoparticles, quantum dots (QDs) are highly appealing due to their manipulatable surfaces, yielding multifunctional QDs applicable in different biological models.

Mechanisms underlying the vasorelaxing effects of butylidenephthalide, an active constituent of Ligusticum chuanxiong, in rat isolated aorta.

Butylidenephthalide (BDPH) is one of the most potent vasorelaxants isolated from Ligusticum chuanxiong Hort. The objective of the current study is to investigate the underlying vasorelaxation mechanisms in rat aorta. In 9,11-dideoxy-9alpha,11alpha-methanoepoxyprostaglandin F(2alpha) (U46619) precontracted preparations, endothelium removal, the nitric oxide (NO) synthase inhibitor Nomega-nitro-l-arginine methyl ester (l-NAME) and the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) partially inhibited the BDPH relaxation response to a similar extent.