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首页> 外文期刊>Acta biomaterialia >Reduction biodegradable brushed PDMAEMA derivatives synthesized by atom transfer radical polymerization and click chemistry for gene delivery.
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Reduction biodegradable brushed PDMAEMA derivatives synthesized by atom transfer radical polymerization and click chemistry for gene delivery.

机译：通过原子转移自由基聚合和点击化学合成的还原型可生物降解拉丝PDMAEMA衍生物，用于基因传递。

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摘要

Novel reducible and degradable brushed poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) derivatives were synthesized and evaluated as non-viral gene delivery vectors. First, alkyne-functionalized poly(aspartic acid) with a disulfide linker between the propargyl group and backbone poly([(propargyl carbamate)-cystamine]-α,β-aspartamide) (P(Asp-SS-AL)) was synthesized. Second, linear low molecular weight (LMW) monoazido-functionalized PDMAEMAs synthesized via atom transfer radical polymerization were conjugated to the polypeptide side-chains of P(Asp-SS-AL) via click chemistry to yield high molecular weight (HMW) polyaspartamide-based disulfide-containing brushed PDMAEMAs (PAPDEs). The PAPDEs were able to condense plasmid DNA to form 100 to 200nm polyplexes with positive ζ-potentials. Moreover, in the presence of dithiothreitol the PAPDEs degraded into LMW PDAMEMA, resulting in disintegration of the PAPDE/DNA polyplexes and subsequent release of plasmid DNA. In vitro experiments revealed that the PAPDEs were less cytotoxic and more effective in gene transfection than control 25kDa poly(ethyleneimine) and HMW linear PDMAEMA. In conclusion, reducible and degradable polycations composed of LMW PDMAEMAs coupled to a polypeptide backbone via reduction-sensitive disulfide bonds are effective gene vectors with an excellent cytocompatibility.
机译：合成了新型的可还原和可降解的拉丝聚甲基丙烯酸2-（二甲基氨基）乙酯（PDMAEMA）衍生物，并作为非病毒基因传递载体进行了评估。首先，合成了炔丙基官能化的聚天冬氨酸，其在炔丙基和主链聚（[（氨基甲酸丙炔基酯-胱胺）-α，β-天冬酰胺）（P（Asp-SS-AL））之间具有二硫键。其次，通过点击化学将通过原子转移自由基聚合合成的线性低分子量（LMW）单叠氮基官能化的PDMAEMA偶联到P（Asp-SS-AL）的多肽侧链上，从而得到基于高分子量（HMW）的聚天冬酰胺基含二硫化物的拉丝PDMAEMA（PAPDE）。 PAPDE能够浓缩质粒DNA形成具有正ζ电位的100至200nm多聚体。此外，在二硫苏糖醇的存在下，PAPDEs降解成LMW PDAMEMA，导致PAPDE / DNA多聚体解体并随后释放质粒DNA。体外实验表明，与对照25kDa聚乙烯亚胺和HMW线性PDMAEMA相比，PAPDEs的细胞毒性较小，在基因转染中更有效。总之，由LMW PDMAEMA组成的可还原和可降解的聚阳离子通过还原敏感的二硫键与多肽主链偶联，是具有出色细胞相容性的有效基因载体。

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