چاپ صفحه |  صفحه نخست سامانه |  چکیده مقاله |  نویسندگان |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده ثبت کننده مقاله | نصرت اله ضرغامی |
| مرحله جاری مقاله | تایید نهایی |
| دانشکده/مرکز مربوطه | دانشکده علوم نوین پزشکی |
| کد مقاله | 61668 |
| عنوان فارسی مقاله | Polyelectrolyte complexes of hTERT siRNA and polyethyleneimine: Effect of degree of PEG grafting on biological and cellular activity |
| عنوان لاتین مقاله | Polyelectrolyte complexes of hTERT siRNA and polyethyleneimine: Effect of degree of PEG grafting on biological and cellular activity |
| ناشر | 5 |
| آیا مقاله از طرح تحقیقاتی و یا منتورشیپ استخراج شده است؟ | خیر |
| عنوان نشریه (خارج از لیست فوق) | Artificial Cells, Nanomedicine and Biotechnology |
| نوع مقاله | Original Article |
| نحوه ایندکس شدن مقاله | ایندکس شده سطح یک – ISI - Web of Science |
| آدرس لینک مقاله/ همایش در شبکه اینترنت | http://www.tandfonline.com/doi/abs/10.3109/21691401.2015.1064936 |
| Gene silencing by siRNA (short interfering RNA)-targeted human telomerase reverse transcriptase (hTERT) is considered a successful strategy for cancer gene therapy. Polyelectrolyte complexes (PEC) of siRNA and cationic polymers such as polyethyleneimine (PEI) have been widely used for cellular transfection; however, they demonstrate some disadvantages such as cytotoxicity and extracellular matrix restrictions. PEG grafting technology was used in an attempt to improve the biocompatibility of PECs. Considering that this technology may compromise the cellular uptake of PECs, we aimed to study the eff ect of degree of PEI PEGylation on the carrier cytotoxicity, cellular association, and transfection effi ciency of hTERT siRNA in the lung cancer cell line A549. Activated NHS ester of methoxy PEG – COOH 5 KDa was grafted to hyperbranched PEI 25 KDa in the molar ratios of 0.2 and 1. The copolymers were characterized by 1 H-NMR spectroscopy. PECs of PEI or PEG-g-PEI with siRNA, alone or co-incubated with heparin sulfate, were studied by the ethidium bromide exclusion assay. Cytotoxicity of the polymers (PEG-g-PEI vs PEI), alone and upon formation of PEC nanoparticles with hTERT siRNA, was determined by a validated MTT assay, in comparison to a scrambled control sequence, in A549 human lung carcinoma cells. The cellular uptake of the PECs of FITC-labeled siRNA was investigated by fl ow cytometry at diff erent N/P ratios, and the silencing eff ect of the transfected siRNA was compared to that of the control sequence for diff erent PECs by real time RT-PCR. The cytotoxicity of PEI decreased signifi cantly by PEG grafting, even at a low degree of PEGylation. Moreover, the nonspecifi c cytotoxicity of PECs decreased by PEG grafting. PECs of PEG-g-PEI showed more biologic stability on incubation with heparin sulfate. Average particle size and zeta potential of PEC nanoparticles were diminished for those of PEG-g-PEI. The cellular association was more pronounced at an N/P ratio of 2.5 for PECs of PEI and PEG-g-PEI alike. The level of silencing of hTERT mRNA by PEC of PEG-g-PEI was sequence-dependent, and determined non-inferior when compared to the native PEI. Conclusively, the biocompatibility of PEI was improved by a low degree of PEGylation, with no adverse eff ect on the cellular uptake and the transfection activity. PEC nanoparticles of hTERT siRNA and PEG-g-PEI could act as a promising weapon against A549 cells, which has to be considered for an in vivo evaluation. |
| نویسنده | نفر چندم مقاله |
|---|---|
| نصرت اله ضرغامی | سوم |
| ابوالفضل اکبرزاده | پنجم |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| Polyelectrolyte complexes of hTERT siRNA and polyethyleneimine Effect of degree of PEG grafting on biological and cellular activity.pdf | 1396/08/11 | 488646 | دانلود |
