کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1425283 986760 2011 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Bioreducible polymers with cell penetrating and endosome buffering functionality for gene delivery systems
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Bioreducible polymers with cell penetrating and endosome buffering functionality for gene delivery systems
چکیده انگلیسی

Bioreducible cationic polymers (p(DAHa-R/APIb)s) composed of different ratios (a:b = 2:1, 1:1, 1:2) between arginine-grafted diaminohexane (DAH-R) (cell penetrating functionality) and 1-(3-aminopropyl) imidazole (API) (endosome buffering functionality) monomers were synthesized by Michael reaction of N,N′-cystaminebisacrylamide (CBA) with them, in order to study the effect of endosome buffering moiety on arginine-grafted bioreducible polymeric gene carriers. Several experiments displayed a distinct correlation between monomer composition ratios of p(DAH-R/API)s and the polymer features. Increased endosome buffering capacities proportional to API portions was evaluated for p(DAH-R/API)s due to the imidazole group (pKa = 6) of API. Increased portions of API non-ionized at physiological pH and resultant decrease of arginine residues also reduced cytotoxicities of the polymers due to less interaction of cellular compartments with less positively charged polymers but decreased pDNA condensing abilities, Zeta-potential values, cellular uptakes of polyplexes, and finally transfection efficiencies as well. Thus, the predominance of arginine residues over endosome buffering moieties was revealed regarding efficient gene delivery for p(DAH-R/API)s. From transfection results with chloroquine or nigericin, it can be deduced that the endosomal escape of p(DAH-R/API) polyplexes occurs by direct endosome membrane penetration of arginine moieties as well as endosome buffering of the polymers after cellular uptake, which emphasizes the importance of arginine moieties for polymeric gene delivery systems.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 152, Issue 1, 30 May 2011, Pages 110–119
نویسندگان
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