Investigation of Metal-Organic Framework-5 (MOF-5) as an Antitumor Drug Oridonin Sustained Release Carrier

Abstract

Oridonin (ORI) is a natural active ingredient with strong anticancer activity. But its clinical use is restricted due to its poor water solubility, short half-life, and low bioavailability. The aim of this study is to utilize the metal organic framework material MOF-5 to load ORI in order to improve its release characteristics and bioavailability. Herein, MOF-5 was synthesized by the solvothermal method and direct addition method, and characterized by Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectrometer (FTIR), Thermogravimetric Analysis (TG), Brunauer-Emmett-Teller (BET), and Dynamic Light Scattering (DLS), respectively. MOF-5 prepared by the optimal synthesis method was selected for drug-loading and in vitro release experiments. HepG2 cells were model cells. MTT assay, 4',6-diamidino-2-phenylindole (DAPI) staining and Annexin V/PI assay were used to detect the biological safety of blank carriers and the anticancer activity of drug-loaded materials. The results showed that nano-MOF-5 prepared by the direct addition method had complete structure, uniform size and good biocompatibility, and was suitable as an ORI carrier. The drug loading of ORI@MOF-5 was 52.86% ± 0.59%. The sustained release effect was reliable, and the cumulative release rate was about 87% in 60 h. ORI@MOF-5 had significant cytotoxicity (IC50:22.99 μg/mL) and apoptosis effect on HepG2 cells. ORI@MOF-5 is hopeful to become a new anticancer sustained release preparation. MOF-5 has significant potential as a drug carrier material.

Keywords: Antitumor; HepG2 cells; MOF-5; Oridonin; sustained release.

Figure 1

Chemical structure of oridonin.

Figure 2

Schematic illustration of the construction of metal organic framework material (MOF-5).

Figure 3

The flow chart for synthesis, drug-loading, and in vitro release.

Figure 4

Characterization of MOF-5 synthesized by two methods: (A) Scanning Electron Microscopy (SEM) Image of MOF-5-S; (B) SEM Image of MOF-5-D; (C) X-ray diffraction (XRD) patterns of MOF-5-S and MOF-5-D (D) Fourier Transform Infrared Spectrometer (FTIR) spectra of MOF-5-S and MOF-5-D; (E) Thermogravimetric (TG) analysis of MOF-5-S and MOF-5-D.

Figure 5

Particle size distribution of MOF-5-S (A) and MOF-5-D (B); (C) Brunauer–Emmett–Teller (BET) isotherm of MOF-5-S and MOF-5-D at 77 K.

Figure 6

(A) FTIR spectra of ORI and ORI@MOF-5; (B) TG analysis of ORI and ORI@MOF-5; (C) XRD patterns of ORI@MOF-5; (D) BET isotherm of ORI@MOF-5.

Figure 7

(A) The cumulative release of ORI from ORI@MOF-5 at three pH values; (B) Fitting results of equation.

Figure 8

(A) Cytotoxicity study of MOF-5 on HepG2 cells determined by MTT assay; (B) Fluorescent microscopic images of DAPI-stained HepG2 cells following 24-h treatment with different concentrations of MOF-5.

Figure 9

(A) Apoptosis assays for HepG2 cells after treatment with different concentrations of MOF-5 for 24 h; (B) Statistical analysis of cell apoptosis.

Figure 10

(A) In vitro cell viabilities of HepG2 cells after being incubated for 24 h with various concentrations of ORI and ORI@MOF-5; (B) Fluorescence microscopic images of HepG2 cells stained with DAPI after 24-h treatment with ORI@MOF-5 (at IC50 value).

Figure 11

(A) Apoptosis assays for HepG2 cells after treatment with different concentrations of ORI@MOF-5 for 24 h; (B) Statistical analysis of viable, necrotic, and apoptotic HepG2 cells.