Redondo Juan Alfonso, Martínez-Campos Enrique, Plet Laetitia, Pérez-Perrino Mónica, Navarro Rodrigo, Corrales Guillermo, Pandit Abhay, Reinecke Helmut, Gallardo Alberto, López-Lacomba José Luis, Fernández-Mayoralas Alfonso, Elvira Carlos
Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006, Madrid, Spain.
Institute of Biofunctional Studies (IEB), Tissue Engineering Group, (UCM), Associated Unit to the Institute of Polymer Science and Technology (CSIC), Paseo de Juan XXIII 1, 28040, Madrid, Spain.
Macromol Rapid Commun. 2016 Apr;37(7):575-83. doi: 10.1002/marc.201500647. Epub 2016 Feb 2.
The incorporation of cyclodextrins (CDs) to nonviral cationic polymer vectors is very attractive due to recent studies that report a clear improvement of their cytocompatibility and transfection efficiency. However, a systematic study on the influence of the CD derivatization is still lacking. In this work, the relevance of β-CD permethylation has been addressed by preparing and evaluating two series of copolymers of the cationic N-ethyl pyrrolidine methacrylamide (EPA) and styrenic units bearing pendant hydroxylated and permethylated β-CDs (HCDSt and MeCDSt, respectively). For both cell lines, CDs permethylation shows a strong influence on plasmid DNA complexation, "in vitro" cytocompatibility and transfection efficiency of the resulting copolymers over two murine cell lines. While the incorporation of the hydroxylated CD moiety increased the cytotoxicity of the copolymers in comparison with their homopolycationic counterpart, the permethylated copolymers have shown full cytocompatibility as well as superior transfection efficiency than the controls. This behavior has been related to the different chemical nature of both units and tentatively to a different distribution of units along the polymeric chains. Cellular internalization analysis with fluorescent copo-lymers supports this behavior.
由于最近的研究报告称环糊精（CDs）与非病毒阳离子聚合物载体结合后其细胞相容性和转染效率有明显提高，因此这种结合非常具有吸引力。然而，目前仍缺乏关于CD衍生化影响的系统研究。在这项工作中，通过制备和评估阳离子N-乙基吡咯烷甲基丙烯酰胺（EPA）与带有侧链羟基化和全甲基化β-CD的苯乙烯单元（分别为HCDSt和MeCDSt）的两个系列共聚物，探讨了β-CD全甲基化的相关性。对于这两种细胞系，CDs全甲基化对所得共聚物与两种小鼠细胞系的质粒DNA络合、“体外”细胞相容性和转染效率有很大影响。与同聚阳离子对应物相比，羟基化CD部分的掺入增加了共聚物的细胞毒性，而全甲基化共聚物表现出完全的细胞相容性以及比对照更高的转染效率。这种行为与两种单元的不同化学性质有关，并初步与单元沿聚合物链的不同分布有关。用荧光共聚物进行的细胞内化分析支持了这种行为。
