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首页> 外文期刊>Nanotechnology >Targeting etoposide to acute myelogenous leukaemia cells using nanostructured lipid carriers coated with transferrin
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Targeting etoposide to acute myelogenous leukaemia cells using nanostructured lipid carriers coated with transferrin

机译：使用涂有转铁蛋白的纳米结构脂质载体将依托泊苷靶向急性骨髓性白血病细胞

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The aim of the present study was to evaluate the diverse properties of transferrin (Tf)-conjugated nanostructured lipid carriers (NLCs) prepared using three different fatty amines, including stearylamine (SA), dodecylamine (DA) and spermine (SP), and two different methods for Tf coupling. Etoposide-loaded NLCs were prepared by an emulsion-solvent evaporation method followed by probe sonication. Chemical coupling of NLCs with Tf was mediated by an amide linkage between the surface-exposed amino group of the fatty amine and the carboxyl group of the protein. The physical coating was performed in a Ringer-Hepes buffer medium. NLCs were characterized by their particle size, zeta potential, polydispersity index, drug entrapment percentage, drug release profiles and Tf-coupling efficiency. The cytotoxicity of NLCs on K562 acute myelogenous leukaemia cells was studied by MTT assay, and their cellular uptake was studied by a flow cytometry method. SA-containing NLCs showed the lowest particle size, the highest zeta potential and the largest coupling efficiency values. The drug entrapment percentage and the zeta potential decreased after Tf coupling, but the average particle size increased. SP-containing formulations released their drug contents comparatively slower than SA- or DA-containing NLCs. Unconjugated NLCs released moderately more drug than Tf-NLCs. Flow cytometry studies revealed enhanced cellular uptake of Tf-NLCs compared to unconjugated ones. Blocking Tf receptors resulted in a significantly higher cell survival rate for Tf-NLCs. The highest cytotoxic activity was observed in the chemically coupled SA-containing nanoparticles, with an IC50 value of 15-fold lower than free etoposide.
机译：本研究的目的是评估使用三种不同的脂肪胺（包括硬脂胺（SA），十二烷基胺（DA）和精胺（SP））制备的转铁蛋白（Tf）-缀合的纳米结构脂质载体（NLC）的多样性。 Tf耦合的不同方法。负载依托泊苷的NLC是通过乳液-溶剂蒸发法，然后进行探针超声处理制备的。 NLC与Tf的化学偶联是通过脂肪胺表面暴露的氨基与蛋白质的羧基之间的酰胺键介导的。物理涂布在林格-海普斯缓冲液中进行。 NLC的特征在于其粒径，ζ电位，多分散指数，药物截留率，药物释放曲线和Tf耦合效率。通过MTT法研究了NLCs对K562急性骨髓性白血病细胞的细胞毒性，并通过流式细胞术研究了其细胞摄取。含SA的NLC显示出最低的粒径，最高的Zeta电位和最大的耦合效率值。 Tf偶联后，药物截留率和ζ电势降低，但平均粒径增加。含SP的制剂释放其药物含量要比含SA或DA的NLC慢。未结合的NLC比Tf-NLC释放出更多的药物。流式细胞术研究表明，与未结合的Tf-NLC相比，Tf-NLC的细胞吸收增强。阻断Tf受体可显着提高Tf-NLC的细胞存活率。在化学偶联的含SA纳米颗粒中观察到最高的细胞毒活性，其IC50值比游离依托泊苷低15倍。

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