In vitro targeted therapy on human hepatic carcinoma cells using folate-functionilazed sorafenib-loaded magnetic polymeric micelles

Abstract

Objective To evaluate the tumor targeting characteristic and the inhibitory effect to human hepatic carcinoma cells (HepG2 cells) of the folate-superparamagnetic iron oxide (SPIO)-sorafenib-micelles (targeted micelles) by in vitro studies.Methods First of all,the synthesis of targeted micelles was completed and the folate-free sorafenib-micelles (non-targeted micelles) were used as control.Cell suspensions were incubated with the polymeri micelles with different sorafenib concentrations (10.0000,5.0000,2.5000,1.2500,0.6250,0.3125 lμmol/L) for 1 h.Prussian blue staining was performed to show intracellular irons.The inhibitory effect on HepG2 cells proliferation in vitro was assessed by methyl thiazolyl tetrazolium (MTT) assay and the apoptotic rate of the treated cells were detected by flow cytometry.Results Prussian blue staining showed much more intracellular iron in cells incubated with targeted micelles than nontargeted micelles.MTT assay showed that the average inhibitive ratio in the folate group and the folate-free group were 38.13％ and 22.54％ (P ＜0.05).The mean apoptotic rate of treated cells in the folate group,the folate-free group and the control group were 17.01％,11.04％ and 7.89％,and the apoptotic rate in the folate group was higher than the folate-free group (P ＜ 0.05).Conclusion Targeted micelles have better targeting tropism to the hepatic carcinoma cells in vitro than non-targeted micelles and show the effect in inhibiting the proliferation and inducing apopotisis of HepG2 cells in vitro. Key words: Folic acid; Sorafenib; Nanomicelles; Targeted therapy