Cyclodextrin‐Based Star‐Like Amphiphilic Cationic Polymer as a Potential Pharmaceutical Carrier in Macrophages,Macromolecular Rapid Communications

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Cyclodextrin‐Based Star‐Like Amphiphilic Cationic Polymer as a Potential Pharmaceutical Carrier in Macrophages
Macromolecular Rapid Communications ( IF 4.2 ) Pub Date : 2018-05-28 , DOI: 10.1002/marc.201800207
Hongwei Cheng ₁ , Xiaoshan Fan ₂ , Caisheng Wu ₁ , Xiaoyuan Wang ₁ , Li-Juan Wang ₁ , Xian Jun Loh ₃ , Zibiao Li ₃ , Yun-Long Wu ₁

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Effective delivery of therapeutic genes or small molecular drugs into macrophages is important for cell based immune therapy, but it remains a challenge due to the intracellular reactive oxygen species and endosomal degradation of therapeutics inside immune cells. In this report, the star‐like amphiphilic biocompatible β‐cyclodextrin‐graft‐(poly(ε‐caprolactone)‐block‐poly(2‐(dimethylamino) ethyl methacrylate)_x (β‐CD‐g‐(PCL‐b‐PDMAEMA)_x) copolymer, consisting of a biocompatible cyclodextrin core, hydrophobic poly(ε‐caprolactone) PCL segments and hydrophilic PDMAEMA blocks with positive charge, is optimized to achieve high efficiency gene transfection with enhanced stability, due to the micelle formation by hydrophobic PCL segments. In comparison with lipofetamine, a currently popular nonviral gene carrier, β‐CD‐g‐(PCL‐b‐PDMAEMA)_x copolymer, shows better transfection efficiency of plasmid desoxyribose nucleic acid in RAW264.7 macrophages. More interestingly, this delivery platform by β‐CD‐g‐(PCL‐b‐PDMAEMA)_x not only shows low toxicity but also better dexamethasone delivery efficiency, which might indicate its great potential in immunotherapy.

中文翻译：

基于环糊精的星形两亲性阳离子聚合物作为巨噬细胞的潜在药物载体

有效治疗基因或小分子药物向巨噬细胞的有效传递对基于细胞的免疫治疗很重要，但由于细胞内活性氧和免疫细胞内部治疗剂的内体降解，仍然是一项挑战。在该报告中，星形的两亲性的生物相容性β-cyclodextrin-接枝- （聚（ε -己内酯） -嵌段-聚（2-（二甲基氨基）乙基甲基丙烯酸酯）_X（β-CD-克- （PCL- b -PDMAEMA ）_x）共聚物由生物相容性环糊精核心，疏水性聚（ε-己内酯）PCL片段和带正电荷的亲水性PDMAEMA嵌段组成，由于疏水性PCL片段形成了胶束，因此经过优化可实现具有增强稳定性的高效基因转染。与Lipofetamine相比，目前流行的非病毒基因载体β-CD- g-（PCL - b- PDMAEMA）_x共聚物在RAW264.7巨噬细胞中表现出更好的质粒脱氧核糖核酸转染效率。更有趣的是，该交付平台由β-CD- g-（PCL - b- PDMAEMA）_x 不仅显示出低毒性，而且地塞米松的递送效率更高，这可能表明其在免疫治疗中的巨大潜力。

更新日期：2018-05-28

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