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一种新型的 HA 涂层纳米粒子共包封质粒 METase 和 5-Fu 的设计,显示出在靶向胃癌干细胞中的应用增强。

A novel design of HA-coated nanoparticles co-encapsulating plasmid METase and 5-Fu shows enhanced application in targeting gastric cancer stem cells.

机构信息

Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No.1 Minde Road, Donghu District, Nanchang 330006, Jiangxi, China.

出版信息

Biol Chem. 2018 Feb 23;399(3):293-303. doi: 10.1515/hsz-2017-0208.

DOI:10.1515/hsz-2017-0208
PMID:29016350
Abstract

Nanoparticles (NPs) are recognized as an attractive vehicles for cancer treatment due to their targeted drug release. Gastric cancer is an important killer disease, and its therapy methods still need improvement. The NPs were prepared using a precipitation method, and were evaluated using transmission electron microscopy (TEM). MTT and Transwell assays were used to determine cell viability and apoptosis. In vivo experiments were performed to validate the effects of NPs on tumor growth. Methioninase (METase)/5-Fu co-encaspulated NPs showed highest ζ size and lowest ζ potential than other NPs. The migration and tumorsphere formation ability of CD44(+) was stronger than CD44(-). The effects of METase/5-Fu co-encaspulated NPs on inhibition cell growth was stronger than that of 5-Fu encaspulated NPs, while HA coated NPs showed significant target ability than that NPs without HA. METase supplementation promoted the inhibition effect of 5-Fu on thymidylate synthetase (TS), as well as cell apoptosis. The in vivo experiments demonstrated that HA coated NPs significantly inhibited tumor growth. It was concluded that HA-coated NPs enhance the target ability, while METase/5-Fu co-encaspulated NPs promote the inhibition effects on tumor growth in gastric cancer.

摘要

纳米粒子(NPs)由于其靶向药物释放而被认为是癌症治疗的有吸引力的载体。胃癌是一种重要的致命疾病,其治疗方法仍需改进。使用沉淀法制备 NPs,并使用透射电子显微镜(TEM)进行评估。MTT 和 Transwell 测定用于确定细胞活力和细胞凋亡。进行体内实验以验证 NPs 对肿瘤生长的影响。甲硫氨酸酶(METase)/5-Fu 共包封 NPs 的 ζ 尺寸最大, ζ 电位最低,优于其他 NPs。CD44(+)的迁移和肿瘤球形成能力强于 CD44(-)。METase/5-Fu 共包封 NPs 对抑制细胞生长的作用强于 5-Fu 包封 NPs,而 HA 包被的 NPs 比没有 HA 的 NPs 具有明显的靶向能力。METase 补充促进了 5-Fu 对胸苷酸合成酶(TS)的抑制作用以及细胞凋亡。体内实验表明,HA 包被的 NPs 显著抑制了肿瘤生长。结论是,HA 包被的 NPs 增强了靶向能力,而 METase/5-Fu 共包封 NPs 促进了对胃癌肿瘤生长的抑制作用。

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