Development of an MRI-visible nonviral vector for siRNA delivery targeting gastric cancer

Abstract

An antibody-directed nonviral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles and a gastric cancer-associated CD44v6 single-chain variable fragment (scFv_CD44v6,-PEG-g-PEI-SPION), was constructed as a gastric cancer-targeting and magnetic resonance imaging (MRI)-visible nanocarrier for small interfering RNA (siRNA) delivery. Biophysical characterization of PEG-g-PEI-SPION and scFv_CD44v6-PEG-g-PEI-SPION was carried out, including siRNA condensation capacity, cell viability, and transfection efficiency. Both the targeting and nontargeting nanocarriers were effective for transferring siRNA in vitro. The cellular uptake and distribution of nanoparticles complexed with siRNA was analyzed by fluorescence imaging and immunofluorescent staining. Moreover, the gastric cancer-targeting effect was verified in vivo by MRI and histology analysis. These results indicate that scFv_CD44v6-PEG-g-PEI-SPION is a promising nonviral vector for gastric cancer gene therapy and diagnosis.

Keywords:

• tumor targeting
• CD44 variant 6
• nonviral vector
• small interfering RNA
• magnetic resonance imaging

Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81072045, 30670951 and 50830107), the Natural Science Foundation of Guangdong Province (Grant No. 6021322 and 9351027501000003), and the Industry-University-Research Foundation of Guangdong Province, China (Grant No. 2009B090300277).

Disclosure

The authors report no conflicts of interest in this work.