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

Gongsen Chen,Yibo Wang,Xingbin Yin,Yingchao Yu,Mengru Cai,Liuying Qin,Lili Gao,Pingqing Huang,Jian Ni,Xiaoxv Dong,Juyuan Luo,Yangming Ding

doi:10.3390/molecules24183369

Gongsen Chen, Yibo Wang + Show 10 more

Open Access

https://doi.org/10.3390/molecules24183369

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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.

Highlights

It is expected that cancer will be the main cause of death and the most important obstacle to increasing life expectancy in every country in the world in the twenty-first century [1]
Our results indicate that metal organic frameworks (MOFs)-5, which synthesized by direct biosafetyaddition, of MOF-5 antitumor activity after drug-loading were examined byeffects
Was slowly synthesized in a high temperature and pressure environment, while MOF-5-D was rapidly grown within a few hours by adding TEA

Summary

Introduction

It is expected that cancer will be the main cause of death and the most important obstacle to increasing life expectancy in every country in the world in the twenty-first century [1]. In 2018, there were 18.1 million incident cancer cases and 9.6 million cancer deaths worldwide. Cancer cases increased by 29.5% between 2006 and 2018. The incidence and mortality rates for lung cancer, breast cancer, prostate cancer, colorectal cancer, stomach cancer, and liver cancer are among the highest [2]. Cancer treatment methods are relatively simple and have large side effects. It is very necessary to study new anti-tumor active ingredients and drug delivery systems to improve the efficacy and reduce the side effects of cancer treatment

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