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The decrease of PAMAM dendrimer-induced cytotoxicity by PEGylation via attenuation of oxidative stress

机译：通过降低氧化应激，通过PEG化降低PAMAM树状聚合物诱导的细胞毒性

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摘要

Due to their unique structure, poly(amidoamine) (PAMAM) dendrimers have been widely used in medical applications. However, PAMAM dendrimers bearing amino terminals show certain cytotoxicity. In order to improve their biocompatibility, we modified Generation-5 PAMAM dendrimers by conjugating them with poly(ethylene glycol) (PEG) of two different molecular weights and different number of chains. The IC50 values of PEGylated dendrimers were 12-105 fold higher than those of PAMAM dendrimers. To investigate the influence of PEGylation on PAMAM-induced cytotoxicity, the intracellular responses, reactive oxygen species (ROS) content, mitochondrial membrane potential (MMP), and apoptosis were examined. The results indicated that conjugation with PEG could effectively reduce the PAMAM-induced cell apoptosis by attenuating the ROS production and inhibiting PAMAM-induced MMP collapse. Meanwhile, dendrimers conjugated with less PEG of lower molecular weight did not significantly change the endocytic properties. Dendrimers conjugated with more PEG of higher molecular weight were much less cytotoxic. This study provided a novel insight into the effects of PEGylation on the decrease of cytotoxicity at the molecular level.
机译：由于其独特的结构，聚（酰胺基胺）（PAMAM）树状聚合物已广泛用于医疗应用。但是，带有氨基末端的PAMAM树状聚合物显示出一定的细胞毒性。为了提高它们的生物相容性，我们通过将它们与两种分子量和不同链数的聚乙二醇（PEG）偶联来修饰了Generation-5 PAMAM树状聚合物。 PEG化树状聚合物的IC50值比PAMAM树状聚合物的IC50值高12-105倍。要研究聚乙二醇化对PAMAM诱导的细胞毒性的影响，检查了细胞内应答，活性氧（ROS）含量，线粒体膜电位（MMP）和凋亡。结果表明，与PEG的缀合可以通过减弱ROS产生并抑制PAMAM诱导的MMP崩溃而有效地减少PAMAM诱导的细胞凋亡。同时，与较少的较低分子量的PEG缀合的树枝状聚合物没有显着改变内吞特性。与更高分子量的更多PEG缀合的树状聚合物的细胞毒性要小得多。这项研究提供了新的见解在分子水平上聚乙二醇化对减少细胞毒性的影响。

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