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首页> 外文期刊>Acta biomaterialia >Influence of hydroxyl groups on the biological properties of cationic polymethacrylates as gene vectors
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Influence of hydroxyl groups on the biological properties of cationic polymethacrylates as gene vectors

机译：羟基对阳离子聚甲基丙烯酸酯作为基因载体的生物学特性的影响

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In this study poly(aminoethyl methacrylate) (PAEMA), poly(3-amino-2-hydroxypropyl methacrylate) (PAHPMA), poly(2-(2-aminoethylamino)ethyl methacrylate) (PAEAEMA) and poly(3-(2-aminoethylami-no) 2-hydroxypropyl methacrylate) (PAEAHPMA) were synthesized using atom transfer radical polymerization to evaluate the effect of hydroxyl groups on the relative properties of cationic polymeric gene vectors. The results of heparin displacement assays showed that PAHPMA possessed a stronger binding capacity than PAEMA. PAHPMA/DNA complexes and PAEAHPMA/DNA complexes had lower zeta potentials than those of PAEMA and PAEAEMA. MTT assay results indicated that PAHPMA and PAEAHPMA exhibited obviously lower cytotoxicities than PAEMA and PAEAEMA. Subsequently, in vitro gene transfec-tion studies in 293T cells without serum showed that PAHPMA exhibited a lower transfection efficiency than PAEMA and PAEAHPMA/DNA complexes possessed a similar transfection efficiency to PAEAEMA/ DNA complexes. Moreover, PAHPMA and PAEAHPMA retained similar transfection efficiencies in DMEM with 10% serum, but PAEMA and PAEAEMA showed slightly lower transfection efficiencies than in the absence of serum. The reason for these phenomena might be attributed to the introduction of hydroxyl groups into PAHPMA and PAEAHPMA, i.e. the existence of hydroxyl groups might increase the binding capacity to DNA and at the same time decrease the surface charge of the polymer/DNA complexes due to the formation of hydrogen bonds between the polymers and DNA. Therefore, a lower zeta potential and stronger binding ability may result in a lower gene transfection efficiency. This effect of hydroxyl groups decreased with increasing amino group density on the polymer.
机译：在这项研究中，聚（甲基丙烯酸氨基乙酯）（PAEMA），聚（甲基丙烯酸3-氨基-2-羟丙酯）（PAHPMA），聚（甲基丙烯酸2-（2-氨基乙基氨基）乙酯）（PAEAEMA）和聚（3-（2-通过原子转移自由基聚合反应合成了氨基乙基氨基（甲基丙烯酸2-羟丙酯）（PAEAHPMA），以评估羟基对阳离子聚合基因载体相对性质的影响。肝素置换试验的结果表明，PAHPMA的结合能力强于PAEMA。 PAHPMA / DNA复合物和PAEAHPMA / DNA复合物的ζ电势低于PAEMA和PAEAEMA。 MTT分析结果表明，PAHPMA和PAEAHPMA的细胞毒性明显低于PAEMA和PAEAEMA。随后，在无血清的293T细胞中进行体外基因转染研究表明，PAHPMA的转染效率低于PAEMA，并且PAEAHPMA / DNA复合物的转染效率与PAEAEMA / DNA复合物相似。此外，PAHPMA和PAEAHPMA在含有10％血清的DMEM中保留了相似的转染效率，但是PAEMA和PAEAEMA的转染效率比没有血清的情况略低。这些现象的原因可能归因于在PAHPMA和PAEAHPMA中引入了羟基，即羟基的存在可能增加与DNA的结合能力，同时降低聚合物/ DNA复合物的表面电荷。在聚合物和DNA之间形成氢键。因此，较低的ζ电位和较强的结合能力可能导致较低的基因转染效率。羟基的这种作用随着聚合物上氨基密度的增加而降低。

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