State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China; Haihe Laboratory of Modern Chinese Medicine, Tianjin 301617, P.R. China; Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China.
State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China; Haihe Laboratory of Modern Chinese Medicine, Tianjin 301617, P.R. China.
Int J Biol Macromol. 2023 Jun 15;240:124370. doi: 10.1016/j.ijbiomac.2023.124370. Epub 2023 Apr 11.
Stimulus-responsive nanomaterials have become a hot spot in controllable drug delivery systems researches owing to their spatiotemporal controllable properties based on the differences between tumor microenvironment and normal tissue. Herein, iron (III) carboxylate metal-organic framework nanoparticles coated with glycyrrhetinic acid-chitosan conjugate (MIL-101/GA-CS) were successfully fabricated and acted as the pH-responsive and target-selective system to deliver doxorubicin (DOX) for hepatocellular carcinoma (HCC) therapy. The prepared nanocarrier possess the advantages of uniform size, comparable drug loading efficiency (28.89%), and superior pH-dependent controlled drug release (DOX release of 2.74% and 89.18% within 72 h at pH 7.4 and 5.5, respectively). In vitro cytotoxicity assays showed that the drug-loaded nanocarriers exhibited excellent inhibitory effects on HepG2 cells due to the sustained release of DOX, while the nanocarriers showed no significant toxicity. Furthermore, cell uptake experiments demonstrated that MIL-101-DOX/GA-CS could target HepG2 cells based on receptor-dependent internalization of glycyrrhetinic acid receptors mediated. In vitro 3D hepatoma cell microspheres experiments showed that MIL-101-DOX/GA-CS had excellent penetration and tumor killing ability. Therefore, MIL-101-DOX/GA-CS nanoparticles have a prospective application in cancer therapy as a pH-responsive controlled drug delivery system.
基于肿瘤微环境与正常组织之间的差异，具有时空可控性能的刺激响应型纳米材料在可控药物传递系统的研究中成为热点。在此，成功制备了负载甘草次酸-壳聚糖偶联物的铁（III）羧酸金属-有机骨架纳米粒子（MIL-101/GA-CS），并将其用作 pH 响应型和靶向选择性系统，用于肝细胞癌（HCC）治疗的阿霉素（DOX）递送。所制备的纳米载体具有均匀的尺寸、相当的药物负载效率（28.89%）和优越的 pH 依赖性控制药物释放（在 pH 7.4 和 5.5 下 72 h 内分别释放 2.74%和 89.18%的 DOX）的优点。体外细胞毒性试验表明，由于 DOX 的持续释放，载药纳米载体对 HepG2 细胞表现出优异的抑制作用，而纳米载体无明显毒性。此外，细胞摄取实验表明，基于甘草次酸受体介导的受体依赖性内化，MIL-101-DOX/GA-CS 可以靶向 HepG2 细胞。体外 3D 肝癌细胞微球实验表明，MIL-101-DOX/GA-CS 具有优异的穿透和肿瘤杀伤能力。因此，MIL-101-DOX/GA-CS 纳米粒子作为 pH 响应型控制药物传递系统，在癌症治疗方面具有广阔的应用前景。
