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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.
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页码:809 / 821
页数:13
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