Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2021; 27(26): 4208-4220
Published online Jul 14, 2021. doi: 10.3748/wjg.v27.i26.4208
Metal-organic framework IRMOFs coated with a temperature-sensitive gel delivering norcantharidin to treat liver cancer
Xiu-Yan Li, Qing-Xia Guan, Yu-Zhou Shang, Yan-Hong Wang, Shao-Wa Lv, Zhi-Xin Yang, Rui Wang, Yu-Fei Feng, Wei-Nan Li, Yong-Ji Li
Xiu-Yan Li, Qing-Xia Guan, Yu-Zhou Shang, Yan-Hong Wang, Shao-Wa Lv, Zhi-Xin Yang, Rui Wang, Yu-Fei Feng, Wei-Nan Li, Yong-Ji Li, College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjiang Province, China
Author contributions: Li XY, Guan QX, Shang YZ, Wang YH, Lv SW, Yang ZX, Wang R, Feng YF, Li WN, and Li YJ performed the experiments and acquired and analyzed the data; Li XY, Guan QX, Shang YZ, and Wang YH wrote the manuscript; All authors approved the final version of the article.
Supported by National Natural Science Foundation of China, No. 82074025 and No. 82074271; the Heilongjiang Traditional Chinese Medicine Research Project, No. ZHY18-047; and Scientific Research Project of Heilongjiang Health Committee, No. 2020-293.
Institutional review board statement: This study was approved by Ethics Committee of Heilongjiang University of Chinese Medicine, Harbin, China.
Conflict-of-interest statement: The authors report no conflicts of interest in this work.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Yong-Ji Li, PhD, Professor, College of Pharmacy, Heilongjiang University of Chinese Medicine, No. 24 Heping Road, Xiangfang District, Harbin 150040, Heilongjiang Province, China.
Received: February 25, 2021
Peer-review started: February 25, 2021
First decision: April 18, 2021
Revised: April 27, 2021
Accepted: May 27, 2021
Article in press: May 27, 2021
Published online: July 14, 2021
Research background

Norcantharidin (NCTD) is suitable for the treatment of primary liver cancer, especially early and middle primary liver cancer. As a new type of drug formulation, sustained- and controlled-release preparations can increase the efficacy and reduce the side effects compared with traditional drugs. Metal-organic frameworks (MOFs) have potential applications in drug carriers. The thermosensitive gel has a hydrophilic three-dimensional network structure, which can be loaded in the liquid state to control drug release.

Research motivation

The side effects of NCTD have limited its application in liver cancer, which has prompted the development of sustained- and controlled-release preparations.

Research objectives

This study established a liver-targeting therapy in which NCTD is loaded into IRMOF-3 coated with a thermosensitive gel (NCTD-IRMOF-3-Gel), which can be efficiently delivered to liver cancer cells and slowly released.

Research methods

NCTD-loaded IRMOF-3 coated with a temperature-sensitive gel (NCTD-IRMOF-3-Gel) was obtained by a coordination reaction. The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated. Cell cytotoxicity assays, flow cytometry and apoptosis experiments on mouse hepatoma (Hepa1-6.) cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models.

Research results

The particle size of NCTD-IRMOF-3-Gel was 50-100 nm, and the particle size distribution was uniform. The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect. The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation, and with increasing drug concentrations, the inhibition rate increased. By flow cytometry, NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases, and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest. Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells.

Research conclusions

NCTD-loaded IRMOF-3 nanoparticles incorporated into a thermosensitive gel appeared to be a useful tool for cancer treatment because of the enhanced inhibition rate of cancer cells and controlled release of drugs from these nanocarriers.

Research perspectives

Thermosensitive gel-encapsulated IRMOF-3 has great advantages as an antitumor drug carrier and provides some ideas for passive targeting therapy of tumors.