JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
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Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro.

BACKGROUND: The purpose of this study was to evaluate the inhibitory effect of targeted folate-functionalized micelles containing superparamagnetic iron oxide nanoparticles (SPIONs) and sorafenib on human hepatic carcinoma (HepG2) cells in vitro, and to observe the feasibility of surveillance of this targeting therapeutic effect by magnetic resonance imaging.

METHODS: Sorafenib and SPIONs were loaded into polymeric micelles. The targeted nanocarrier was synthesized by functionalizing the micelles with folate. Folate-free micelles loaded with sorafenib and SPIONs were used as control (nontargeted) micelles. Uptake of the nanocarrier by cells was assessed using Prussian blue staining after 1 hour of incubation with the polymeric micelles. The inhibitory effect of the targeted micelles on HepG2 cell proliferation at various concentrations of sorafenib was assessed in vitro using the methyl thiazolyl tetrazolium (MTT) assay and apoptotic analysis using flow cytometry. Magnetic resonance imaging using a clinical 1.5 T scanner was performed to detect changes in the signal intensity of cells after incubation with the targeted micelles.

RESULTS: Prussian blue staining showed significantly more intracellular SPIONs in cells incubated with the targeted micelles than those incubated with nontargeted micelles. The MTT assay showed that the average inhibitory ratio in the targeted group was significantly higher than that in the nontargeted group (38.13% versus 22.54%, P = 0.028). The mean apoptotic rate in the targeted cells, nontargeted cells, and untreated cells was 17.01%, 11.04%, and 7.89%, respectively. The apoptotic rate in the targeted cells was significantly higher than that in the nontargeted cells (P = 0.043). The T2 signal intensity on magnetic resonance imaging of cells treated with the targeted micelles decreased significantly with increasing concentrations of sorafenib in the cell culture medium, but there was no obvious decrease in signal intensity in cells treated with the nontargeted micelles.

CONCLUSION: Folate-functionalized polymeric micelles loaded with SPIONs and sorafenib inhibited proliferation and induced apoptosis of HepG2 cells in vitro. The inhibitory events caused by targeted micelles can be monitored using clinical magnetic resonance.

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