Department of Gastroenterology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, PR China.
Department of Pathophysiology, School of Basic Medicine Science, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, PR China.
Nanomedicine (Lond). 2018 Apr 1;13(7):769-785. doi: 10.2217/nnm-2017-0345. Epub 2018 Feb 20.
miRNAs have been recognized for their potential in cancer therapeutics, and multiple miRNAs were suggested to affect target genes expression. To overcome limitations of free synthetic miRNAs, such as easily degraded in biofluids and limited in cellular uptake, novel miRNAs delivery systems need to be developed.
MATERIALS & METHODS: Using surface-functionalizing technique, poly(D,L-lactide-co-glycolide)/poly(L-lactide)-block-poly(ethylene glycol)-folate polymer nanoparticle (PLGA/PLA-PEG-FA) loaded with miR-204-5p (FA-NPs-miR-204) was developed. The therapeutic efficacy of FA-NPs-miR-204 was evaluated in the Luc-HT-29 xenograft tumor model in vivo.
FA-NPs-miR-204 could be taken up by HT-29 and HCT-116 cells efficiently, resulting in significant inhibitory effect on cell proliferation and promotive effect on cell apoptosis. In vivo study showed that FA-NPs-miR-204 could exert tumor suppressive function in Luc-HT-29 xenograft model.
Our study demonstrates a convenient miRNA delivery system that targets tumor tissue and exerts tumor suppressive function, thus demonstrating a potential new therapeutic option for colon cancer.
miRNA 在癌症治疗中的潜力已得到认可,多个 miRNA 被认为可以影响靶基因的表达。为了克服游离合成 miRNA 的局限性,如在生物流体中容易降解和细胞摄取有限,需要开发新型 miRNA 传递系统。
使用表面功能化技术,制备了负载 miR-204-5p 的聚(D,L-乳酸-co- 乙醇酸)/聚(L-乳酸)-嵌段-聚(乙二醇)-叶酸聚合物纳米颗粒(PLGA/PLA-PEG-FA)(FA-NPs-miR-204)。体内研究采用 Luc-HT-29 异种移植瘤模型评估 FA-NPs-miR-204 的治疗效果。
FA-NPs-miR-204 可以被 HT-29 和 HCT-116 细胞有效摄取,对细胞增殖具有显著的抑制作用,对细胞凋亡具有促进作用。体内研究表明,FA-NPs-miR-204 可以在 Luc-HT-29 异种移植瘤模型中发挥肿瘤抑制作用。
本研究证明了一种靶向肿瘤组织并发挥肿瘤抑制作用的新型 miRNA 传递系统,为结肠癌提供了一种潜在的新治疗选择。