The anti-tumor effect of folate-targeted liposome microbubbles loaded with oridonin as ultrasound-triggered tumor-targeted therapeutic carrier system

Abstract

In this study, folate receptor (FR) targeted liposome microbubbles loaded with oridonin (ORI) (F-LMB-ORI), liposome loaded with ORI (L-ORI) and liposome microbubbles loaded with ORI (LMB-ORI) were prepared. In vitro release properties, cellular uptake and cytotoxicity in HepG-2 cells as well as in vivo antitumor effects in HepG-2 cells tumor-bearing mice of F-LMB-ORI, L-ORI and LMB-ORI were evaluated upon ultrasound exposure. Results showed cytotoxicity assay on F-LMB-ORI gave IC₅₀ of 0.508 ± 0.018 µmol/mL on HepG-2 cells and LMB-ORI; L-ORI gave IC₅₀ of 2.424 ± 0.116 µmol/mL, 3.031 ± 0.122 µmol/mL in vitro, respectively. These drug delivery carriers were able to control the release of ORI. F-LMB-ORI exhibited higher binding to HepG-2 cells in comparison to LMB-ORI and L-ORI. F-LMB-ORI improved antitumor activity of ORI obviously in comparison to L-ORI, LMB-ORI under in vivo ultrasound. After the treatment for 14 d, the tumor inhibition ratio for F-LMB-ORI (the dose of ORI: 1.5 × 10⁻²g·kg⁻¹, once a day) was 87.6%, obviously higher than that of LMB-ORI group, L-ORI group and free ORI (the dose of ORI: 1.5 × 10⁻²g·kg⁻¹, once a day) which were 71.5%, 64.3% and 43.4%, respectively.

Keywords:

• Anti-tumor activity
• folate-targeted liposome microbubbles loaded with oridonin
• oridonin

Acknowledgments

The authors are grateful to Nanjing University of Science and Technology.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding information

The project was supported by Independent Research Program (Chinese National Scientific Research Training Program – 2014).