Metal-organic framework IRMOFs coated with a temperature-sensitive gel delivering norcantharidin to treat liver cancer

金属有机骨架 IRMOF 涂覆温度敏感凝胶,递送去甲斑蝥素治疗肝癌

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作者: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

Aim

To develop a nanomaterial carrier, NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel (NCTD-IRMOF-3-Gel), aiming to improve the anticancer activity of NCTD and reduce the drug dose.

Background

Norcantharidin (NCTD) is suitable for the treatment of primary liver cancer, especially early and middle primary liver cancer. This compound can reduce tumors and improve immune function. However, the side effects of NCTD have limited its application. There is a marked need to reduce the side effects and increase the efficacy of NCTD.

Conclusion

Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.

Methods

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 in mouse hepatoma (Hepa1-6) cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models.

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 the inhibition rate increased with increasing drug concentration. 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.

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