کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10162467 | 1114330 | 2014 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Tuning of Poly-S-Nitrosated Human Serum Albumin as Superior Antitumor Nanomedicine
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کلمات کلیدی
PEGylationhuman serum albumin - آلبومین سرم انسانیDimerization - اندازه گیریMacromolecular drug delivery - تحویل داروی مقوی مولکولیCancer - سرطانDrug delivery system - سیستم تحویل داروAntitumor activity - فعالیت ضد تومورNanoparticles - نانوذراتNitric oxide - نیتریک اکسیدControlled release/delivery - کنترل انتشار / تحویل
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Macromolecules have been developed as carriers of low-molecular-weight drugs in drug delivery systems (DDS) to improve their pharmacokinetic profile or to promote their uptake in tumor tissue via enhanced permeability and retention (EPR) effects. We have previously demonstrated that poly-nitric oxide (NO) conjugated human serum albumin (Poly-SNO-HSA) has the potential to be a DDS carrier capable of accumulating NO in tumors. However, the stability of Poly-SNO-HSA in the circulation has to be improved, and its optimal molecular size for using the EPR effects has to be evaluated. In the present study, we performed two tuning methods for refining Poly-SNO-HSA, namely, pegylation and dimerization. We observed that pegylation enhanced the stability of Poly-SNO-HSA both in vitro and in vivo, and that dimerization of Poly-SNO-HSA enhanced the antitumor activity via more efficient delivery of NO in Colon 26 tumor-bearing mice. Intriguingly, dimerization resulted in a 10 times higher antitumor activity. These data suggest that pegylation and dimerization of Poly-SNO-HSA are very important tuners to optimize NO stability and accumulation, and thereby effect, in tumors. Thus, polyethylene glycol-Poly-SNO-HSA dimer seems to be a very appealing and safe NO carrier and thereby a strong candidate as an antitumor drug in future development of cancer therapeutics.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 103, Issue 7, July 2014, Pages 2184-2188
Journal: Journal of Pharmaceutical Sciences - Volume 103, Issue 7, July 2014, Pages 2184-2188
نویسندگان
Yu Ishima, Jun Fang, Ulrich Kragh-Hansen, Hongzhuan Yin, Long Liao, Naohisa Katayama, Hiroshi Watanabe, Toshiya Kai, Ayaka Suenaga, Hiroshi Maeda, Masaki Otagiri, Toru Maruyama,