Liu Fang, Le Wenjun, Mei Tianxiao, Wang Tiegong, Chen Luguang, Lei Yi, Cui Shaobin, Chen Bingdi, Cui Zheng, Shao Chengwei
Radiology Department of Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China.
Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, People's Republic of China.
Int J Nanomedicine. 2016 May 19;11:2195-207. doi: 10.2147/IJN.S104501. eCollection 2016.
Pancreatic cancer is a highly malignant disease with a 5-year survival rate <5% mainly due to lack of early diagnosis and effective therapy. In an effort to improve the early diagnostic rate of pancreatic cancer, a nanoprobe Fe3O4@SiO2 modified with anti-mesothelin antibody (A-MFS) was prepared to target cells and tumor tissues highly expressing mesothelin in vitro (human pancreatic cancer cell line SW1990) and in vivo (subcutaneously transplanted tumors) studies. The A-MFS probe was successfully prepared and was spherical and uniform with a hydrodynamic diameter between 110 and 130 nm. Cell Counting Kit-8 testing indicated that A-MFS was nontoxic in vitro and in vivo studies. The in vitro study showed that the A-MFS probe specifically targeted SW1990 cells with high mesothelin expression. The in vivo study was conducted in Siemens 3.0 T magnetic resonance imaging. The average T2-weighted signal values of the xenografts were 966.533±31.56 before injecting A-MFS and 691.133±56.84 before injecting saline solution. After injection of 0.1 mL A-MFS via nude mouse caudal vein for 2.5 hours, the average T2-weighted signal of the xenograft decreased by 342.533±42.6. The signal value decreased by -61.233±33.9 and -58.7±19.4 after injection of the saline and Fe3O4@SiO2. The decrease of tumor signal by A-MFS was much more significant than that by saline and Fe3O4@SiO2 (P<0.05). The results demonstrated the high stability and nontoxicity of A-MFS, which effectively targeted pancreatic cancer in vitro and in vivo. A-MFS is a promising agent for diagnosis of pancreatic cancer.
胰腺癌是一种高度恶性的疾病，5年生存率<5%，主要原因是缺乏早期诊断和有效的治疗方法。为了提高胰腺癌的早期诊断率，制备了一种用抗间皮素抗体（A-MFS）修饰的纳米探针Fe3O4@SiO2，用于在体外（人胰腺癌细胞系SW1990）和体内（皮下移植瘤）研究中靶向高表达间皮素的细胞和肿瘤组织。成功制备了A-MFS探针，其呈球形且均匀，流体动力学直径在110至130nm之间。细胞计数试剂盒-8检测表明，A-MFS在体外和体内研究中均无毒。体外研究表明，A-MFS探针特异性靶向高表达间皮素的SW1990细胞。体内研究在西门子3.0T磁共振成像中进行。注射A-MFS前，异种移植瘤的平均T2加权信号值为966.533±31.56，注射生理盐水前为691.133±56.84。经裸鼠尾静脉注射0.1mL A-MFS 2.5小时后，异种移植瘤的平均T2加权信号下降了342.533±42.6。注射生理盐水和Fe3O4@SiO2后，信号值分别下降了-61.233±33.9和-58.7±19.4。A-MFS导致的肿瘤信号下降比生理盐水和Fe3O4@SiO2更显著（P<0.05）。结果表明A-MFS具有高稳定性和无毒性，在体外和体内均能有效靶向胰腺癌。A-MFS是一种有前景的胰腺癌诊断剂。
