Characterization of polyethylene glycol-grafted polyethylenimine and superparamagnetic iron oxide nanoparticles (PEG-g-PEI-SPION) as an MRI-visible vector for siRNA delivery in gastric cancer in vitro and in vivo |
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Authors: | Yinting Chen Guoda Lian Chengde Liao Weiwei Wang Linjuan Zeng Chenchen Qian Kaihong Huang Xintao Shuai |
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Affiliation: | 1. Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510120, China 2. Department of Radiology, The Third Affiliated Hospital of Kunming Medical University, Kunming, 650118, China 3. Center of Biomedical Engineering, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, 510275, China
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Abstract: | Background Gene therapy is a promising therapeutic method but is severely hampered due to its lack of an ideal delivery system. Therefore, in this study, a nonviral and magnetic resonance imaging (MRI) visible vector, polyethylene glycol-grafted polyethylenimine and superparamagnetic iron oxide nanoparticles (PEG-g-PEI-SPION) was used as a nanocarrier for small interfering RNA (siRNA) delivery in gastric cancer. Methods Biophysical characterization of PEG-g-PEI-SPION was systematically analyzed, including size, zeta potential, siRNA condensation capacity, cell viability, transfection efficiency, cellular uptake, and MRI-visible function in vivo. Besides, CD44 variant isoform 6 (CD44v6), a protein marker for metastatic behavior in gastric cancer, and was chose as the target gene to further analyze the siRNA delivery function of PEG-g-PEI-SPION. Results Under comprehensive analysis, the appropriate N/P ratio of PEG-g-PEI-SPION/siRNA was 10,. and siRNA targeting at human CD44v6 (siCD44v6) transferred by PEG-g-PEI-SPION was effective at downregulating the CD44v6 expression of gastric carcinoma cell line SGC-7901 in vitro. Moreover, knockdown of CD44v6 impaired migrating and invasive abilities of SGC-7901 cells. Furthermore, PEG-g-PEI-SPION was a highly efficient contrast agent for MRI scan in vivo. Conclusion PEG-g-PEI-SPION was a promising nonviral vector with molecular image tracing capacity for cancer gene therapy. And CD44v6 was a potential target gene for the prevention and detection of metastatic behavior in gastric cancer. |
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