载顺铂的 AS1411 适体修饰的聚乳酸-羟基乙酸纳米粒用于 miR-21 抑制的卵巢癌细胞的靶向治疗。
AS1411 aptamer-decorated cisplatin-loaded poly(lactic-co-glycolic acid) nanoparticles for targeted therapy of miR-21-inhibited ovarian cancer cells.
机构信息
Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
出版信息
Nanomedicine (Lond). 2018 Nov;13(21):2729-2758. doi: 10.2217/nnm-2018-0205. Epub 2018 Nov 5.
AIM
The overexpression of miRNA-21 correlates with the cisplatin (CIS) resistance in the ovarian cancers.
METHODS
AS1411 antinucleolin aptamer-decorated PEGylated poly(lactic-co-glycolic acid) nanoparticles containing CIS (Ap-CIS-NPs) and anti-miR-21 (Ap-anti-miR-21-NPs) were prepared, physicochemically investigated and their cancer-targeting ability was confirmed. CIS-resistant A2780 cells (A2780 R) were infected with anti-miR-21 using Ap-anti-miR-21-NPs to decrease the drug resistance and sensitize the cells to CIS. Afterward, miR-21-inhibited cells were exposed to the Ap-CIS-NPs.
RESULTS
Ap-anti-miR-21-NPs could infect the A2780 R cells mainly through nucleolin-mediated endocytosis and inhibit the endogenous miR-21. Targeted delivery of CIS using Ap-CIS-NPs into the miR-21-inhibited cells caused an enhanced mortality.
CONCLUSION
The targeted delivery of chemotherapeutics to the oncomiR-inhibited cells may find a robust application in cancer chemo/gene therapy.
目的
miRNA-21 的过表达与卵巢癌中顺铂（cisplatin，CIS）耐药相关。
方法
制备了载有顺铂（cisplatin，CIS）和抗 miR-21（anti-miR-21）的 AS1411 核仁素适体修饰的聚乙二醇化聚（乳酸-共-乙醇酸）纳米颗粒（Ap-CIS-NPs 和 Ap-anti-miR-21-NPs），并对其理化性质进行了研究，同时确认了它们的癌症靶向能力。用 Ap-anti-miR-21-NPs 将抗 miR-21 转染至 CIS 耐药的 A2780 细胞（A2780 R）以降低耐药性并使细胞对 CIS 敏感。随后，将 miR-21 抑制的细胞暴露于 Ap-CIS-NPs 下。
结果
Ap-anti-miR-21-NPs 主要通过核仁素介导的内吞作用感染 A2780 R 细胞，并抑制内源性 miR-21。将 Ap-CIS-NPs 靶向递送至 miR-21 抑制的细胞中递送 CIS 可导致细胞死亡率显著增加。
结论
针对致癌 miRNA 抑制细胞的化学治疗药物靶向递送可能在癌症化疗/基因治疗中具有广泛的应用前景。
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