2. Academic Validation
  3. Metal-organic framework decorated with glycyrrhetinic acid conjugated chitosan as a pH-responsive nanocarrier for targeted drug delivery

Metal-organic framework decorated with glycyrrhetinic acid conjugated chitosan as a pH-responsive nanocarrier for targeted drug delivery

  • Int J Biol Macromol. 2023 Apr 11;240:124370. doi: 10.1016/j.ijbiomac.2023.124370.
Liu Cui 1,  Xi Wang 2,  Zhaoyun Liu 1,  Ziqi Li 1,  Ziwei Bai 1,  Kui Lin 3,  Jian Yang 2,  Yuanlu Cui 4,  Fei Tian 5
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 Analytical Instrumentation Centre, Tianjin University, Tianjin 300072, P.R. China.
  • 4 State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China. Electronic address: cuiyl@tju.edu.cn.
  • 5 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. Electronic address: tianfei.louise@163.com.
PMID: 37044320 DOI: 10.1016/j.ijbiomac.2023.124370
Abstract

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.

Keywords

Drug targeting delivery; Metal organic framework; Receptor-dependent internalization; pH-responsive.

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