Optimization of Tet1 ligand density in HPMA-co-oligolysine copolymers for targeted neuronal gene delivery.
Optimization of Tet1 ligand density in HPMA-co-oligolysine copolymers for targeted neuronal gene delivery.
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DOI：
10.1016/j.biomaterials.2013.08.045
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发表时间：
2013-12
期刊：
影响因子：
14
通讯作者：
Pun, Suzie H.
中科院分区：
文献类型：
--
作者：
Chu, David S. H.;Schellinger, Joan G.;Bocek, Michael J.;Johnson, Russell N.;Pun, Suzie H.
靶向基因递送载体可以增强细胞特异性和转染效率。我们以前证明，Tet 1，结合到GT 1b神经节苷脂的肽，聚乙烯亚胺的共轭结果在体内的神经祖细胞的优先转染。在这项工作中，我们研究Tet 1配体密度对基因递送到神经元样分化的PC-12细胞的影响。通过Tet 1和低聚赖氨酸大分子单体与N-（2-羟丙基）甲基丙烯酰胺（HPMA）的一锅可逆加成-断裂链转移（RAFT）聚合，合成了一系列统计的、含有不同量（1- 5mol%）Tet 1的阳离子肽基聚合物。当与质粒DNA复合时，所得到的Tet 1官能化聚合物组形成的颗粒具有与用非靶向HPMA-寡聚赖氨酸共聚物形成的颗粒相似的颗粒尺寸。使用具有中间Tet 1肽掺入的聚合物观察到神经元样分化的PC-12细胞中的最高细胞摄取。与非靶向聚合物相比，Tet 1最佳掺入的聚合物将基因递送到神经元样PC-12细胞增加了一个数量级以上，但与对照聚合物相比，在转染NIH/3 T3对照细胞中没有效果。
Targeted gene delivery vectors can enhance cellular specificity and transfection efficiency. We demonstrated previously that conjugation of Tet1, a peptide that binds to the GT1b ganglioside, to polyethylenimine results in preferential transfection of neural progenitor cells in vivo. In this work, we investigate the effect of Tet1 ligand density on gene delivery to neuron-like, differentiated PC-12 cells. A series of statistical, cationic peptide-based polymers containing various amounts (1—5 mol%) of Tet1 were synthesized via one-pot reversible addition-fragmentation chain transfer (RAFT) polymerization by copolymerization of Tet1 and oligo-l-lysine macromonomers with N-(2-hydroxypropyl)methacrylamide (HPMA). When complexed with plasmid DNA, the resulting panel of Tet1-functionalized polymers formed particles with similar particle size as particles formed with untargeted HPMA–oligolysine copolymers. The highest cellular uptake in neuron-like differentiated PC-12 cells was observed using polymers with intermediate Tet1 peptide incorporation. Compared to untargeted polymers, polymers with optimal incorporation of Tet1 increased gene delivery to neuron-like PC-12 cells by over an order of magnitude but had no effect compared to control polymers in transfecting NIH/3T3 control cells.
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DOI：
10.1016/j.jconrel.2011.10.016
发表时间：
2012-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Chu DS;Johnson RN;Pun SH
通讯作者：
Pun SH
DOI：
10.1073/pnas.0405313101
发表时间：
2004-12-14
影响因子：
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影响因子：
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