Preparation, In Vitro, and In Vivo Antitumor Activity of Folate Receptor‐Targeted Nanoliposomes Containing Oridonin

Abstract

Abstract Preclinical Research The expression of the folate receptor (FR) is amplified in many cancer types. Oridonin (ORI, C20H28O6) is an isolate from Rabdosia rubescens (Hemsl.) Hara that has been used in the treatment of esophageal and hepatic carcinoma for decades. In order to enhance the antitumor potency of ORI, folate‐polyethylene glycol2000‐distearoylphosphatidyleth‐anolamine (folate‐PEG2000‐DSPE) was synthesized to facilitate preparation of FR‐targeted liposomal ORI (F‐L‐ORI). F‐L‐ORI and PEG2000‐DSPE‐L‐ORI were then prepared. In vitro release properties, cellular uptake, and cytotoxicity in HepG‐2 cells, as well as in vivo potency of the liposomes in murine HepG‐2 tumor‐bearing mice were evaluated. An in vitro cytotoxicity assay on F‐L‐ORI gave an IC50 value of 0.718 ± 0.023 μmol/ml and L‐ORI had an IC50 value of 2.25 ± 0.12 μmol/ml. These liposomes were able to control the release of ORI. In vitro cells binding of F‐L‐ORI exhibited higher binding to HepG‐2 cells as compared with L‐ORI. The antitumor effect studies assessed in vivo showed that F‐L‐ORI improved the antitumor activity of ORI as compared with L‐ORI and free drug. The tumor inhibition ratio for F‐L‐ORI (1.5 × 10−2 g/kg/d) was 85.6%, higher than that of L‐ORI group (1.5 × 10−2 g/kg/d) and free ORI (1.5 × 10−2 g/kg/d) that were 66.8% and 40.8%, respectively.