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Reduction of polyethylenimine-coated iron oxide nanoparticles induced autophagy and cytotoxicity by lactosylation

机译:还原聚乙烯亚胺包覆的氧化铁纳米颗粒通过乳糖基化诱导自噬和细胞毒性

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摘要

Superparamagnetic iron oxide (SPIO) nanoparticles are excellent magnetic resonance contrast agents and surface engineering can expand their applications. When covered with amphiphilic alkyl-polyethyleneimine (PEI), the modified SPIO nanoparticles can be used as MRI visible gene/drug delivery carriers and cell tracking probes. However, the positively charged amines of PEI can also cause cytotoxicity and restricts their further applications. In this study, we used lactose to modify amphiphilic low molecular weight polyethylenimine (C12-PEI2K) at different lactosylation degree. It was found that the N-alkyl-PEI-lactobionic acid wrapped SPIO nanocomposites show better cell viability without compromising their labelling efficacy as well as MR imaging capability in RAW 264.7 cells, comparing to the unsubstituted ones. Besides, we found the PEI induced cell autophagy can be reduced via lactose modification, indicating the increased cell viability might rely on down-regulating autophagy. Thus, our findings provide a new approach to overcome the toxicity of PEI wrapped SPIO nanocomposites by lactose modification.
机译:超顺磁性氧化铁(SPIO)纳米颗粒是出色的磁共振造影剂,表面工程可以扩大其应用范围。当被两亲性烷基-聚乙烯亚胺(PEI)覆盖时,修饰的SPIO纳米颗粒可用作MRI可见基因/药物输送载体和细胞跟踪探针。但是,PEI带正电荷的胺也可能引起细胞毒性,并限制了其进一步的应用。在这项研究中,我们使用乳糖在不同的乳糖基化度下修饰两亲性低分子量聚乙烯亚胺(C12-PEI2K)。发现与未取代的N-烷基-PEI-乳糖酸包裹的SPIO纳米复合材料在RAW 264.7细胞中显示出更好的细胞生存力,而不损害其标记效力以及MR成像能力。此外,我们发现PEI诱导的细胞自噬可以通过乳糖修饰而减少,这表明增加的细胞活力可能依赖于下调自噬。因此,我们的发现提供了一种新方法,通过乳糖修饰克服了PEI包裹的SPIO纳米复合材料的毒性。

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