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Local delivery of neurotrophic factors is a pillar of neural repair strategies in the peripheral nervous system. The main disadvantage of the free growth factors is their short half-life of few minutes. In order to prolong their activity, we have conjugated to iron oxide nanoparticles three neurotrophic factors: nerve growth factor (βNGF), glial cell-derived neurotrophic factor (GDNF), and basic fibroblast growth factor (FGF-2). Comparative stability studies of free versus conjugated factors revealed that the conjugated neurotrophic factors were significantly more stable in tissue cultures and in medium at 37°C.The biological effects of free versus conjugated neurotrophic factors were examined on organotypic dorsal root ganglion (DRG) cultures performed in NVR-Gel, composed mainly of hyaluronic acid and laminin. Results revealed that the conjugated neurotrophic factors enhanced early nerve fiber sprouting compared to the corresponding free factors. The most meaningful result was that conjugated-GDNF, accelerated the onset and progression of myelin significantly earlier than the free GDNF and the other free and conjugated factors. This is probably due to the beneficial and long-acting effect that the stabilized conjugated-GDNF had on neurons and Schwann cells. These conclusive results make NVR-Gel enriched with conjugated-GDNF, a desirable scaffold for the reconstruction of severed peripheral nerve. [ABSTRACT FROM AUTHOR]

Protein aggregation into amyloid fibrils is implicatedin the pathogenesisof many neurodegenerative diseases. Engineered nanoparticles haveemerged as a potential approach to alter the kinetics of protein fibrillationprocess. Yet, there are only a few reports describing the use of nanoparticlesfor inhibition of amyloid-β 40 (Aβ40) peptideaggregation, involved in Alzheimer’s disease (AD). In the presentstudy, we designed new uniform biocompatible amino-acid-based polymernanoparticles containing hydrophobic dipeptides in the polymer sidechains. The dipeptide residues were designed similarly to the hydrophobiccore sequence of Aβ. Poly(N-acryloyl-l-phenylalanyl-l-phenylalanine methyl ester) (polyA-FF-ME)nanoparticles of 57 ± 6 nm were synthesized by dispersion polymerizationof the monomer A-FF-ME in 2-methoxy ethanol, followed by precipitationof the obtained polymer in aqueous solution. Cell viability assayconfirmed that no significant cytotoxic effect of the polyA-FF-MEnanoparticles on different human cell lines, e.g., PC-12 and SH-SY5Y,was observed. A significantly slow secondary structure transitionfrom random coil to β-sheets during Aβ40fibrilformation was observed in the presence of these nanoparticles, resultingin significant inhibition of Aβ40fibrillation kinetics.However, the polyA-FF-ME analogous nanoparticles containing the l-alanyl-l-alanine (AA) dipeptide in the polymer sidegroups, polyA-AA-ME nanoparticles, accelerate the Aβ40fibrillation kinetics. The polyA-FF-ME nanoparticles and the polyA-AA-MEnanoparticles may therefore contribute to a mechanistic understandingof the fibrillation process, leading to the development of therapeuticstrategies against amyloid-related diseases. [ABSTRACT FROM AUTHOR]

Maghemite (gamma-Fe(2)O(3)) magnetic nanoparticles of 15.0 +/- 2.1 nm were formed by nucleation followed by controlled growth of maghemite thin films on gelatin-iron oxide nuclei. Human insulin amyloid fibrils were formed by incubating the monomeric insulin dissolved in aqueous continuous phase at pH 1.6 and 65 degrees C. Magnetic human insulin amyloid fibrils/gamma-Fe(2)O(3) nanoparticle assemblies were prepared by interacting the gamma-Fe(2)O(3) nanoparticles with the insulin amyloid fibrils during or after their formation. The nanoparticles attached selectively to the insulin fibrils in both cases. The kinetics of the insulin fibrillation process in the absence and the presence of the gamma-Fe(2)O(3) nanoparticles was elucidated. The insulin amyloid fibrils/gamma-Fe(2)O(3) nanoparticle assemblies were easily extracted from the aqueous phase via a magnetic field. We hypothesize that this selective extraction approach may also be applicable for the removal of other amyloidogenic proteins that lead to neurodegenerative diseases (e.g., Alzheimer's, Parkinson's, Huntington's, mad cow, and prion diseases) from their continuous phase, e.g. milk, blood, neurological fluid, etc., ((c) 2008 Wiley Periodicals, Inc.)

Early diagnosis in Alzheimer's disease (AD), before the onset of marked clinical symptoms, is critical in preventing the irreversible neuronal damage that eventually leads to dementia and ultimately death. Therefore, there is an urgent need for in vivo imaging agents, which are valuable as specific biomarkers to demonstrate the location and density of amyloid plaques in the living human brain. The present manuscript describes a novel method for selective marking of Abeta(40) fibrils by non-fluorescent gamma-Fe(2)O(3) and fluorescent-magnetic gamma-Fe(2)O(3)-rhodamine or gamma-Fe(2)O(3)-Congo red nanoparticles, and the complete removal of the magnetized fibrils from the aqueous continuous phase by a magnetic field. These fluorescent-maghemite nanoparticles as multimodal imaging agents have a great advantage due to the combination of the magnetic and fluorescence imaging into one nanostructured system. This hybrid system, which selectively marks Abeta(40) fibrils, might enable the early detection of plaques using both MRI and fluorescence microscopy, and therefore may be applied in in vivo AD diagnosis studies. These fluorescent-magnetic nanoparticles may also be useful as selective biomarkers to detect the location and the removal of other amyloid plaques derived from different amyloidogenic proteins that lead to neurodegenerative diseases, e.g., Parkinson's, Huntington's, mad cow, and prion diseases.