Published online Jul 14, 2021. doi: 10.3748/wjg.v27.i26.4208
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
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.
The side effects of NCTD have limited its application in liver cancer, which has prompted the development of sustained- and controlled-release preparations.
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.
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.
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.
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.
Thermosensitive gel-encapsulated IRMOF-3 has great advantages as an antitumor drug carrier and provides some ideas for passive targeting therapy of tumors.