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Autophagy inhibitior autophagy-related 7 small interfering RNA and doxorubicin dual-loaded nanostructured lipid carrier to combat multidrug resistance
Journal of Materials Research ( IF 2.7 ) Pub Date : 2020-11-25 , DOI: 10.1557/jmr.2020.223
Liwen Zhang , Bowen Xu

The multidrug resistance (MDR) is a widely observed phenotype that contributed to the major obstacle of impairing the outcome of cancer chemotherapy. With the aim to reverse MDR in the breast cancer cell line, the autophagy-related 7 (ATG7) small interfering RNA (siRNA) capable of downregulating the cellular autophagy level was loaded into a cationic nanostructured lipid carrier (NLC) with doxorubicin (Dox) to build a platform (NLC/D-R) for effective chemotherapy of breast cancer. Our results revealed that NLC/D-R was well-dispersed nanoparticles with satisfy protection to siRNA. In addition, NLC/D-R also exerted a sufficient drug release of both cargos under an acidic environment with high stability and biocompatibility at the physiological environment. Furthermore, NLC/D-R showed a preferable transfection profile to PEI 25k. The downregulated autophagy level in NLCF-7/Adr cells resulted in reverse of MDR and accumulated Dox retention in cells. The in vitro cytotoxicity using both cells on flat surfaces and multicellular tumor spheroid (NLCTS) model confirmed that NLC/D-R showed much elevated anticancer performance than NLC/Dox or NLC/siRNA, which suggested the synergistic effect between anti-autophagy and chemotherapy.



中文翻译:

自噬抑制或自噬相关的7种小干扰RNA和阿霉素双重负载的纳米结构脂质载体,可抵抗多药耐药性

多药耐药性(MDR)是一种广泛观察到的表型,是造成癌症化疗结果受损的主要障碍。为了逆转乳腺癌细胞系中的MDR,将能够下调细胞自噬水平的自噬相关7(ATG7)小干扰RNA(siRNA)装入带有阿霉素(Dox)的阳离子纳米结构脂质载体(NLC)中建立有效治疗乳腺癌的平台(NLC / DR)。我们的结果表明,NLC / DR是分散良好的纳米颗粒,对siRNA具有令人满意的保护作用。此外,NLC / DR还可以在酸性环境下在生理环境下具有高稳定性和生物相容性的情况下,充分释放两种货物的药物。此外,NLC / DR对PEI 25k表现出较好的转染特性。NLCF-7 / Adr细胞中的自噬水平下调导致MDR逆转并累积了Dox在细胞中的滞留。的使用平坦表面上的细胞和多细胞肿瘤球体(NLCTS)模型进行的体外细胞毒性证实,NLC / DR显示出比NLC / Dox或NLC / siRNA更高的抗癌性能,这表明抗自噬和化学疗法之间具有协同作用。

更新日期:2020-11-25
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