Influence of hydrophilicity of cationic polymers on the biophysical properties of polyelectrolyte complexes formed by self-assembly with DNA
Influence of hydrophilicity of cationic polymers on the biophysical properties of polyelectrolyte complexes formed by self-assembly with DNA
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DOI：
10.1016/s0304-4165(00)00076-3
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发表时间：
2000-07-26
影响因子：
3
通讯作者：
Seymour, LW
中科院分区：
文献类型：
--
作者：
Howard, KA;Dash, PR;Seymour, LW
为了研究制备具有延伸的非颗粒结构的电荷中性基因递送复合物的可能性，允许DNA与一系列含有季电荷甲基丙烯酸三甲基铵乙基酯的亲水性阳离子聚合物自组装（TMAEM，5、15、50、100摩尔%）与亲水性N-（2-羟丙基）甲基丙烯酰胺（HPMA，分别为95、85、50、0摩尔%）共聚。使用溴化乙锭荧光评估，共聚物都能够结合DNA，尽管具有低TMAEM含量的共聚物不排出溴化乙锭。增加共聚物的TMAEM含量改变了复合物的形态，从延伸的（5-15摩尔% TMAEM），通过部分凝聚的颗粒（50摩尔%）离散的纳米颗粒（100摩尔% TMAEM）。基于具有低TMAEM含量（5-50摩尔%）的共聚物的复合物显示出比使用100摩尔% TMAEM（57.8+/-8.2 mV）形成的那些更低的对核酸酶降解的抗性和更低的表面电荷（21.2+/-5.9-45.1+/-3.9 mV）。它们还显示出与体外吞噬细胞的相关性显著降低（人白细胞，摄取降低高达92.3%;小鼠腹腔巨噬细胞，摄取降低高达69.6%），尽管在体内其肝脏蓄积仅轻微降低（最大降低27.6%）。找到亲水性和稳定性的适当平衡是开发用于基因递送的有效载体的关键。(C)2000 Elsevier Science B. V.保留所有权利。
To investigate the possibility of producing charge-neutral gene delivery complexes with extended, non-particulate structures, DNA was allowed to self-assemble with a series of hydrophilic cationic polymers containing quaternary charged trimethylammonio ethylmethacrylate (TMAEM, 5, 15, 50, 100 mol%) copolymerised with hydrophilic N-(2-hydroxypropyl)methacrylamide (HPMA, 95, 85, 50, 0 mol%, respectively). Copolymers were all able to bind DNA, assessed using ethidium bromide fluorescence, although copolymers with low TMAEM content did not expel ethidium bromide. Increasing TMAEM content of the copolymers changed the morphology of the complexes from extended (5-15 mol% TMAEM), through partially condensed particles (50 mol%) to discrete nanoparticles (100 mol% TMAEM). Complexes based on copolymers with low TMAEM content (5-50 mol%) showed less resistance to degradation by nucleases and lower surface charge (21.2+/-5.9-45.1+/-3.9 mV) than those formed using 100 mol% TMAEM (57.8+/-8.2 mV). They also showed significantly less association with phagocytic cells in vitro (human leucocytes, uptake decreased by up to 92.3%; murine peritoneal macrophages, uptake decreased by up to 69.6%), although in vivo their hepatic accumulation was only slightly decreased (maximum decrease 27.6%). Finding the appropriate balance of hydrophilicity and stability is key to development of effective vectors for gene delivery. (C) 2000 Elsevier Science B.V. All rights reserved.