کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10613316 | 986879 | 2005 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Protection of oligonucleotides against nucleases by pegylated and non-pegylated liposomes as studied by fluorescence correlation spectroscopy
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
مهندسی مواد
بیومتریال
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Protection of oligonucleotides against nucleases by pegylated and non-pegylated liposomes as studied by fluorescence correlation spectroscopy Protection of oligonucleotides against nucleases by pegylated and non-pegylated liposomes as studied by fluorescence correlation spectroscopy](/preview/png/10613316.png)
چکیده انگلیسی
Antisense phosphodiester oligonucleotides (ONs), complexed to carriers such as cationic liposomes, inhibit the production of proteins. The biochemical and biophysical phenomena that govern the extent of this inhibition are still not fully understood. Major biological barriers limiting a pronounced antisense effect are the cellular entry and endosomal escape of the ONs containing liposomes, the release of the ONs from the liposomes and the extra- and intracellular degradation of the ONs. In this paper we focus on the latter barrier and evaluate, by fluorescence correlation spectroscopy (FCS), to what extent phosphodiester ONs complexed to DOTAP/DOPE liposomes, are protected against degradation by nucleases. Liposomes studied were either with or without a polyethyleneglycol (PEG) moiety at the surface. Using non-pegylated liposomes the phosphodiester ONs were initially adequately protected when exposed to DNase I. Indeed, in the mechanism for lipoplex formation as suggested by others, the ONs become trapped between lipid bilayers and are therefore shielded from the environment. However, after a few hours the phosphodiester ONs no longer stayed intact. This was explained by a gradual fusion of the lipoplexes in time thereby spontaneously releasing phosphodiester ONs. Using pegylated liposomes, a substantial fraction of the phosphodiester ONs degraded immediately after exposing the complexes to DNase I. Based on experimental evidence we suggest that the presence of the PEG-chains influences lipoplex formation so that the ONs are not trapped between lipid bilayers and therefore remain accessible by the DNase I enzyme.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 110, Issue 1, 10 December 2005, Pages 212-226
Journal: Journal of Controlled Release - Volume 110, Issue 1, 10 December 2005, Pages 212-226
نویسندگان
K. Remaut, B. Lucas, K. Braeckmans, N.N. Sanders, J. Demeester, S.C. De Smedt,