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首页> 美国卫生研究院文献>International Journal of Nanomedicine >Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance
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Intracellular targeted co-delivery of shMDR1 and gefitinib with chitosan nanoparticles for overcoming multidrug resistance

机译：shMDR1和吉非替尼与壳聚糖纳米粒子的细胞内靶向共输送可克服多药耐药性

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摘要

Nowadays, multidrug resistance and side effects of drugs limit the effectiveness of chemotherapies in clinics. P-glycoprotein (P-gp) (MDR1), as a member of the ATP-binding cassette family, acts on transporting drugs into cell plasma across the membrane of cancer cells and leads to the occurrence of multidrug resistance, thus resulting in the failure of chemotherapy in cancer. The main aims of this research were to design a nanodelivery system for accomplishing the effective co-delivery of gene and antitumor drug and overcoming multidrug resistance effect. In this study, shMDR1 and gefitinib-encapsulating chitosan nanoparticles with sustained release, small particle size, and high encapsulation efficiency were prepared. The serum stability, protection from nuclease, and transfection efficiency of gene in vitro were investigated. The effects of co-delivery of shMDR1 and gefitinib in nanoparticles on reversing multidrug resistance were also evaluated by investigating the cytotoxicity, cellular uptake mechanism, and cell apoptosis on established gefitinib-resistant cells. The results demonstrated that chitosan nanoparticles entrapping gefitinib and shMDR1 had the potential to overcome the multidrug resistance and improve cancer treatment efficacy, especially toward resistant cells.
机译：如今，多药耐药性和药物的副作用限制了化学疗法在临床中的有效性。 P-糖蛋白（P-gp）（MDR1）是ATP结合盒家族的一员，可将药物跨癌细胞膜转运到细胞血浆中，并导致多药耐药性的发生，从而导致失败在癌症中的化学疗法。这项研究的主要目的是设计一种纳米传递系统，以完成基因和抗肿瘤药物的有效共同传递，并克服多药耐药性效应。在这项研究中，制备了具有持续释放，小粒径和高包封效率的shMDR1和吉非替尼包封的壳聚糖纳米颗粒。研究了血清的稳定性，核酸酶的保护作用以及基因的体外转染效率。还通过研究已建立的吉非替尼耐药细胞的细胞毒性，细胞摄取机制和细胞凋亡，评估了纳米颗粒中shMDR1和吉非替尼共同递送对逆转多药耐药性的作用。结果表明，包埋吉非替尼和shMDR1的壳聚糖纳米粒子具有克服多药耐药性和提高癌症治疗功效的潜力，尤其是对耐药细胞的治疗效果。

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