School of Pharmacy, Liaoning University, Shenyang 110036, People's Republic of China. Liaoning Key Laboratory of New Drug Research & Development, Shenyang 110036, People's Republic of China.
Nanotechnology. 2020 Aug 7;31(32):325602. doi: 10.1088/1361-6528/ab8c03. Epub 2020 Apr 22.
Liver cancer remains a major cause of cancer-related death across the globe. Nano medicines have emerged as promising candidates to improve liver cancer chemotherapy. In this study, a glycyrrhetinic acid (GA) modified metal-organic framework-based drug delivery system (GA-MOFs) was developed to enhance the liver targeting ability of 5-FU. The physicochemical properties of GA-MOFs regarding particle size, size distribution and morphology were evaluated. The results showed that the obtained 5-FU@GA-MOFs had an octahedral structure, a uniform particle size distribution, and a diameter of ∼200 nm. In vitro release experiments demonstrated that 5-FU@GA-MOFs exhibited a pH-dependent release pattern. MTT assays indicated that 5-FU-loaded GA-MOFs showed greater cytotoxicity towards HepG2 cells when compared to 5-FU alone at the same dose. In vivo tissue distribution demonstrated that the 5-FU@GA-MOFs significantly increased the accumulation of 5-FU in the liver. In vivo imaging analysis further manifested the liver targeting ability of GA-MOFs. Taken together, these results suggested that GA-modified MOFs showed promising potential as liver-targeting nanocarriers for the delivery of anti-tumor drugs.
肝癌仍然是全球癌症相关死亡的主要原因。纳米药物已成为改善肝癌化疗的有前途的候选药物。在这项研究中，开发了一种甘草次酸（GA）修饰的基于金属有机骨架的药物传递系统（GA-MOFs），以增强 5-FU 的肝靶向能力。评估了 GA-MOFs 的物理化学性质，包括粒径、粒径分布和形态。结果表明，所得到的 5-FU@GA-MOFs 具有八面体结构、均匀的粒径分布和约 200nm 的直径。体外释放实验表明，5-FU@GA-MOFs 表现出 pH 依赖性释放模式。MTT 测定表明，与相同剂量的单独 5-FU 相比，负载 5-FU 的 GA-MOFs 对 HepG2 细胞的细胞毒性更大。体内组织分布表明，5-FU@GA-MOFs 显著增加了肝脏中 5-FU 的蓄积。体内成像分析进一步证明了 GA-MOFs 的肝靶向能力。总之，这些结果表明，GA 修饰的 MOFs 作为用于递送抗肿瘤药物的肝靶向纳米载体具有很大的潜力。
