Department of Cardiology, Chinese PLA General Hospital, Beijing, 100853, China.
Nanoscale. 2014 Nov 6;6(23):14343-53. doi: 10.1039/c4nr03003f.
miRNA-16 (miR16) plays an important role in modulating the drug resistance of SGC7901 cell lines to adriamycin (ADR). A variety of viral carriers have been designed for miRNA delivery. However, the safety concerns are currently perceived as hampering the clinical application of viral vector-based therapy. Herein a type of magnetic nanoparticles (MNPs) was designed and synthesized using poly(ethylene glycol) (PEG)-coated Fe₃O₄ nanoparticles as a miRNA delivery system for the purpose of reducing drug resistance of gastric cancer cells by enforcing miR16 expression in SGC7901/ADR cells. The MNPs with good biocompatibility were synthesized by thermal decomposition, and then conjugated with miRNA via electrostatic interaction producing miR16/MNPs. After co-culture with miR16/MNPs, ADR-induced apoptosis of SGC7901/ADR was examined by MTT and TUNEL. miR16/MNPs treatment significantly increased cell apoptosis in vitro. SGC7901/ADR(fluc) tumor-bearing nude mice under ADR therapy were treated with miR16/MNPs by tail vein injection for in vivo study. After intraperitoneal injection of ADR, tumor volume measurement and fluorescence imaging were performed to for the death of SGC7901/ADR cells in vivo. Results showed that miR16/MNPs were able to significantly suppress SGC7901/ADR tumor growth, probably through increasing SGC7901/ADR cells' sensitivity to ADR. Our results suggest the efficient delivery of miR16 by MNPs as a novel therapeutic strategy for drug resistant tumor treatment.
miRNA-16 (miR16) 在调节 SGC7901 细胞系对阿霉素 (ADR) 的耐药性方面发挥着重要作用。已经设计了多种病毒载体来输送 miRNA。然而,目前人们认为安全问题阻碍了基于病毒载体的治疗的临床应用。本文设计并合成了一种磁性纳米粒子 (MNP),该纳米粒子使用聚乙二醇 (PEG) 包裹的 Fe₃O₄ 纳米粒子作为 miRNA 递送系统,旨在通过增强 SGC7901/ADR 细胞中的 miR16 表达来降低胃癌细胞的耐药性。通过热分解合成了具有良好生物相容性的 MNP,然后通过静电相互作用将 miRNA 与 MNP 连接,产生 miR16/MNP。与 miR16/MNP 共培养后,通过 MTT 和 TUNEL 检测 ADR 诱导的 SGC7901/ADR 细胞凋亡。miR16/MNP 处理显著增加了体外细胞凋亡。在 ADR 治疗下,SGC7901/ADR(fluc)荷瘤裸鼠通过尾静脉注射 miR16/MNP 进行体内研究。腹腔注射 ADR 后,进行肿瘤体积测量和荧光成像,以检测体内 SGC7901/ADR 细胞的死亡情况。结果表明,miR16/MNP 能够显著抑制 SGC7901/ADR 肿瘤生长,可能是通过增加 SGC7901/ADR 细胞对 ADR 的敏感性。我们的结果表明,MNP 能够有效地递送 miR16,为耐药性肿瘤治疗提供了一种新的治疗策略。