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 IC of 0.508 ± 0.018 µmol/mL on HepG-2 cells and LMB-ORI; L-ORI gave IC 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 × 10g·kg, 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 × 10g·kg, once a day) which were 71.5%, 64.3% and 43.4%, respectively.

Biocompatible Fe-Based Micropore Metal-Organic Frameworks as Sustained-Release Anticancer Drug Carriers

“…Despite the strong anticancer activity of Ori, its poor solubility in water or common oil, moderate hydrophobicity, chemical instability, and short biological half-life, all limit its clinical use. Moreover, when it is dissolved, the light and heat may lead to active group (α-methylene-cyclopentanone) destruction, further limiting its practical applicability [ 11 , 12 ]. Therefore, finding a new drug carrier to increase the stability of oridonin and improve its in vivo efficiency is important for expanding its clinical anti-tumor applications.…”

Functional graphene oxide as cancer-targeted drug delivery system to selectively induce oesophageal cancer cell apoptosis

“…Oridonin, the main pharmacological active substance of rabdosia rubescens with various pharmacological and physiological effects, has drawn a rising attention for cancer biologists due to its remarkable anti-poliferative and pro-apoptotic effects [11][12][13]. However, the potential application oridonin as an anticancer drug is limited by several factors, such as its insolubility and unfavourable bioavailability, which result in the need for high doses [14,15]. More importantly, oridonin could nonselectively diffuse into tumour and normal cells resulting low therapeutic efficiency with increased side effects [16,17].…”

Solubility and Bioavailability Enhancement of Oridonin: A Review

“…The in vitro inhibition rate of HepG2 cells was as high as 94.0%. The tumor inhibition rate was 89.4% in mice at a dose of 1.5 × 10 −2 g/kg/day, which was significantly higher than that of the uncoated group (71.5%) [58].…”