Antisense oligodeoxylutudeotide-conjugated hyaluronic Acid/Protamine nanocomplexes for intracellular gene inhibition

被引：46

作者：

Mok, Hyejung ^{[1
]}

Park, Ji Won ^{[1
]}

Park, Tae Gwan ^{[1
]}

机构：

[1] Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea

来源：

BIOCONJUGATE CHEMISTRY | 2007年 / 18卷 / 05期

关键词：

MOLECULAR-WEIGHT PROTAMINE; TRANSFECTION EFFICIENCY; FUSOGENIC PEPTIDE; NUCLEIC-ACIDS; DNA DELIVERY; IN-VIVO; MICELLES; COPOLYMERS; CELLS; SIRNA;

D O I：

10.1021/bc070111o

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Green fluorescent protein (GFP) antisense oligodeoxynucleotide (ODN) was covalently conjugated to hyaluronic acid (HA) via a reducible disulfide linkage, and the HA-ODN conjugate was complexed with protamine to increase the extent of cellular uptake and enhance the gene inhibition efficiency of GFP expression. The HA-ODN conjugate formed more stable polyelectrolyte complexes with prolamine as compared to naked ODN, probably because of its increased charge density. The higher cellular uptake of protamine/HA-ODN complexes than that of protamine/naked ODN complexes was attributed to the formation of more compact nanosized complexes (similar to 200 nm in diameter) in aqueous solution. Protamine/HA-ODN complexes also showed a comparable level of GFP gene inhibition to that of cytotoxic polyethylenimine (PEI)/ODN complexes. Since both HA and prolamine are naturally occurring biocompatible materials, the current formulation based on a cleavable conjugation strategy of ODN to HA could be potentially applied as safe and effective nonviral carriers for ODN and siRNA nucleic acid therapeutics.

引用

页码：1483 / 1489

页数：7

共 33 条

[1] Effect of size and serum proteins on transfection efficiency of poly((2-dimethylamino)ethyl methacrylate)-plasmid nanoparticles [J].

Cherng, JY ;

vandeWetering, P ;

Talsma, H ;

Crommelin, DJA ;

Hennink, WE .

PHARMACEUTICAL RESEARCH, 1996, 13 (07) :1038-1042

[2] Biophysical characterization of PEI/DNA complexes [J].

Choosakoonkriang, S ;

Lobo, BA ;

Koe, GS ;

Koe, JG ;

Middaugh, CR .

JOURNAL OF PHARMACEUTICAL SCIENCES, 2003, 92 (08) :1710-1722

[3] Reducible poly(amido ethylenediamine) for hypoxia-inducible VEGF delivery [J].

Christensen, Lane V. ;

Chang, Chien-Wen ;

Yockman, James W. ;

Conners, Rafe ;

Jackson, Heidi ;

Zhong, Zhiyuan ;

Feijen, Jan ;

Bu, David A. ;

Kim, Sung Wan .

JOURNAL OF CONTROLLED RELEASE, 2007, 118 (02) :254-261

[4] Intracellular tracking of protamine/antisense oligonucleotide nanoparticles and their inhibitory effect on HIV-1 transactivation [J].

Dinauer, N ;

Lochmann, D ;

Demirhan, I ;

Bouazzaoui, A ;

Zimmer, A ;

Chandra, A ;

Kreuter, J ;

von Briesen, H .

JOURNAL OF CONTROLLED RELEASE, 2004, 96 (03) :497-507

[5] Physiochemical properties of low and high molecular weight poly(ethylene glycol)-grafted poly(ethylene imine) copolymers and their complexes with oligonucleotides [J].

Glodde, M ;

Sirsi, SR ;

Lutz, GJ .

BIOMACROMOLECULES, 2006, 7 (01) :347-356

[6] Efficient gene transfer using reversibly cross-linked low molecular weight polyethylenimine [J].

Gosselin, MA ;

Guo, WJ ;

Lee, RJ .

BIOCONJUGATE CHEMISTRY, 2001, 12 (06) :989-994

[7] Recent advances in tumor-targeting anticancer drug conjugates [J].

Jaracz, S ;

Chen, J ;

Kuznetsova, LV ;

Ojima, L .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (17) :5043-5054

[8] Novel intracellular delivery system of antisense oligonucleotide by self-assembled hybrid micelles composed of DNA/PEG conjugate and cationic fusogenic peptide [J].

Jeong, JH ;

Kim, SW ;

Park, TG .

BIOCONJUGATE CHEMISTRY, 2003, 14 (02) :473-479

[9] Strategies for silencing human disease using RNA interference [J].

Kim, Daniel H. ;

Rossi, John J. .

NATURE REVIEWS GENETICS, 2007, 8 (03) :173-184

[10] Comparative evaluation of target-specific GFP gene silencing efficiencies for antisense ODN, synthetic siRNA, and siRNA plasmid complexed with PEI-PEG-FOL conjugate [J].

Kim, SH ;

Mok, H ;

Jeong, JH ;

Kim, SW ;

Park, TG .

BIOCONJUGATE CHEMISTRY, 2006, 17 (01) :241-244

← 1 2 3 4 →