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Luteinizing hormone-releasing hormone targeted poly(methyl vinyl ether maleic acid) nanoparticles for doxorubicin delivery to MCF-7 breast cancer cells

机译:黄体生成素释放激素靶向的聚(甲基乙烯基醚马来酸)纳米颗粒,用于将阿霉素递送至MCF-7乳腺癌细胞

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摘要

The purpose of this study was to design a targeted anti-cancer drug delivery system for breast cancer. Therefore, doxorubicin (DOX) loaded poly(methyl vinyl ether maleic acid) nanoparticles (NPs) were prepared by ionic cross-linking method using Zn2+ ions. To optimise the effect of DOX/polymer ratio, Zn/polymer ratio, and stirrer rate a full factorial design was used and their effects on particle size, zeta potential, loading efficiency (LE, %), and release efficiency in 72 h (RE72, %) were studied. Targeted NPs were prepared by chemical coating of tiptorelin/polyallylamin conjugate on the surface of NPs by using 1-ethyl-3-(3-dimethylaminopropyl) carboiimid HCl as cross-linking agent. Conjugation efficiency was measured by Bradford assay. Conjugated triptorelin and targeted NPs were studied by Fourier-transform infrared spectroscopy (FTIR). The cytotoxicity of DOX loaded in targeted NPs and non-targeted ones were studied on MCF-7 cells which overexpress luteinizing hormone-releasing hormone (LHRH) receptors and SKOV3 cells as negative LHRH receptors using Thiazolyl blue tetrazolium bromide assay. The best results obtained from NPs prepared by DOX/polymer ratio of 5%, Zn/polymer ratio of 50%, and stirrer rate of 960 rpm. FTIR spectrum confirmed successful conjugation of triptorelin to NPs. The conjugation efficiency was about 70%. The targeted NPs showed significantly less IC50 for MCF-7 cells compared to free DOX and non-targeted NPs.
机译:这项研究的目的是设计一种针对乳腺癌的靶向抗癌药物递送系统。因此,使用锌离子通过离子交联法制备了负载阿霉素(DOX)的聚(甲基乙烯基醚马来酸)纳米颗粒(NPs)。为了优化DOX /聚合物比,Zn /聚合物比和搅拌速度的影响,使用了全因子设计,它们对粒径,zeta电位,负载效率(LE,%)和72小时内释放效率(RE72)具有影响,%)进行了研究。通过使用1-乙基-3-(3-二甲基氨基丙基)碳酰二氢呋喃盐酸盐作为交联剂,化学将链霉菌素/聚烯丙胺共轭物涂覆在NP表面上,制备了靶向NP。通过Bradford测定法测量缀合效率。通过傅里叶变换红外光谱(FTIR)研究了结合的曲普瑞林和靶向NP。使用噻唑基蓝四唑鎓溴化试剂盒研究了过表达黄体生成素释放激素(LHRH)受体和SKOV3细胞作为负LHRH受体的MCF-7细胞对靶向NP和非靶向NP中DOX的细胞毒性。由DOX /聚合物比率为5%,Zn /聚合物比率为50%和搅拌器速度为960 rpm制备的NP可获得最佳结果。 FTIR光谱证实曲普瑞林与NPs成功结合。缀合效率为约70%。与自由DOX和非靶向NP相比,靶向NP对MCF-7细胞的IC50明显降低。

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