کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10229329 | 518 | 2013 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Synthesis of TAT peptide-tagged PEGylated chitosan nanoparticles for siRNA delivery targeting neurodegenerative diseases
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی شیمی
بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Delivery of therapeutic molecules to the brain for the treatment of Neurodegenerative diseases (ND) is a challenging task. This manuscript introduces a novel scheme of synthesizing peptide-tagged polyethylene glycol (PEG)ylated chitosan polymer to develop nanoparticles for siRNA delivery for use in ND. Specifically, this manuscript proposes a facile chemoselective conjugation of monomethoxy PEG, at the C2 hydroxyl group of chitosan polymer, with conjugation of PEG to a cell-penetrating peptide, Trans-Activator of Transcription. The synthesized Chitosan-PEG-TAT polymer was used to form the nanoparticles of approximately 5Â nm, complexing siRNA to be delivered in neuronal cells (Neuro 2a), with no/minimal toxicity. The various intermediates and the final product formed during the synthesis were characterized using 1H Nuclear Magnetic Resonance and Fourier Transform Infrared Spectroscopy spectra. The morphological details of the nanoparticles were studied using Transmission Electron Microscopy. The nanoparticles were tested to deliver a functional siRNA against the Ataxin-1 gene in an in-vitro established model of a ND Spinocerebellar ataxia (SCA1) over-expressing ataxin protein. The results indicate successful suppression of the SCA1 protein following 48Â h of transfection. Result of this study has potential in ND like SCA, Parkinson's, Alzheimer's and others.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 34, Issue 4, January 2013, Pages 1270-1280
Journal: Biomaterials - Volume 34, Issue 4, January 2013, Pages 1270-1280
نویسندگان
Meenakshi Malhotra, Catherine Tomaro-Duchesneau, Satya Prakash,