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Ularly promising due to their high surface area to volume ratio

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작성자 Don 작성일 24-04-12 08:31 조회 5 댓글 0

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Ularly promising due to their high surface area to volume ratio, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/22026160 magnetic properties, biocompatibility, relative non-toxicity, and biodegradability. The use of iron oxide magnetic nanoparticles for various biomedical applications, e.g., hyperthermia, diagnosis, cell-labeling and sorting, DNA separation, MRI contrast agents and drug delivery, have already been demonstrated [30-35]. In this study, we present a novel approach for specific inhibition of microglial cells in rTg4510 tau-transgenic mice by using fibrin 377-395 peptide-conjugated -Fe2O3 nanoparticles of 21 ?3.5 nm diameter. The stabilization of the peptide by its conjugation to these nanoparticles significantly decreased the number of the microglial cells compared to the same concentration of the free peptide. Furthermore, the specific inhibition of microglial cells, attained using the 377-395 peptide-conjugated -Fe2O3 nanoparticles, was found to have a dual effect on tau pathology depending on the age of the mice used in the study.ResultsSpecific inhibition of microglial cells using fibrin 377-395 peptide-conjugated -Fe2O3 nanoparticlesThe fibrin derived 377-395 peptide has been shown to specifically 4-Bromo-5-nitro-1H-indazole inhibit microglial activity in vivo [28] and was therefore chosen to facilitate the specific inhibitionGlat et al. Journal of Nanobiotechnology 2013, 11:32 http://www.jnanobiotechnology.com/content/11/1/Page 3 ofof microglial activity. This PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/13867361 peptide, however, possesses a short half-life when administered in saline solution and needs to be administered constantly as a result. To counteract this issue, we have conjugated the peptide to -Fe2O3 nanoparticles. The transmission electron microscope (TEM) image of the fibrin 377-395 peptideconjugated -Fe2O3 nanoparticles shown in Figure 1 demonstrates that these nanoparticles are stable against agglomeration and possess a diameter of 21 ?3.5 nm. These nanoparticles have been shown to enhance efficacy of delivery of bioactive material and to provide protection against biodegradation [36]. Fibrin 377-395 peptide, once conjugated to the nanoparticles, is retained in the site of injection and does not disperse by diffusion. This was confirmed 30 days post intracranial injection, using potassium ferrocyanide staining, which gave a positive staining with brains treated with the conjugated peptide, whereas no positive staining was seen in brain hemispheres injected with saline or free fibrin 377-395 peptide (Figure 2). To determine the effect of fibrin 377-395 peptide on activation of microglial cells, we measured the average numbers of activated microglial cells per area in animals injected with saline versus fibrin 377-395 peptideconjugated -Fe2O3 nanoparticles, as well as free fibrin 377-395 peptide. We were unable to determine the specificity of fibrin 377-395 peptide-conjugated -Fe2O3 nanoparticles to the microglia. Figure 3 shows examples of activated microglia cells using IB4, a lectin which stains activated microglia. The data were analyzed with a 2-wayanalysis of variance (ANOVA). The fibrin 377-395 peptide, when conjugated to the nanoparticles, significantly reduced the number of activated microglia (white arrows) in the site of injection compared to saline (Figure 3, top 2 rows), (F = 41.01; (degrees of freedom (df) = 1,274; p 0.05). An effect of age was also found (F = 74.89; df = 1,274; p 3-Bromo-5-chloro-2-fluoroaniline 0.05). In addition, we also found an interaction effect between age and treatment (F = 4.25; df = 1,274; p 0.05). These results are summarized i.

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