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

被引:47
作者
Chen, Yinting [1 ]
Lian, Guoda [1 ]
Liao, Chengde [2 ]
Wang, Weiwei [3 ]
Zeng, Linjuan [1 ]
Qian, Chenchen [1 ]
Huang, Kaihong [1 ]
Shuai, Xintao [3 ]
机构
[1] Sun Yat Sen Univ, Affiliated Hosp 2, Dept Gastroenterol, Guangzhou 510120, Peoples R China
[2] Kunming Med Univ, Dept Radiol, Affiliated Hosp 3, Kunming 650118, Peoples R China
[3] Sun Yat Sen Univ, Sch Chem & Chem Engn, Ctr Biomed Engn, Guangzhou 510275, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
Nanoparticulate vector; Magnetic resonance imaging; Small interfering RNA; CD44 variant isoform 6; Gastric cancer; GENE DELIVERY; ADHESION MOLECULES; NONVIRAL VECTOR; INTESTINAL-TYPE; DIFFUSE-TYPE; CD44; EXPRESSION; CELLS; COMPLEXES; THERAPY;
D O I
10.1007/s00535-012-0713-x
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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. 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. 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. 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.
引用
收藏
页码:809 / 821
页数:13
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