Wu Qiong-ya, Shi Jing-yun, Zhang Jie, Zhang Lin-qian, Zhao Yin-min, Tang Liang, Chen Yun, He Xiao-dong, Liu Hui, Su Bo
Department of Radiation Oncology, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai 200433, China.
Email:
Zhonghua Zhong Liu Za Zhi. 2013 Nov;35(11):808-13.
To construct angiogenesis-specific RGD10-NGR9 dual-targeting superparamagnetic iron oxide nanoparticles, and to evaluate its magnetic resonamce imaging (MRI) features in nude mice and potential diagnostic value in tumor MRI.
Dual-targeting peptides RGD10-NGR9 were designed and synthesized. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles were synthesized by chemical co-precipitation method and the surface was modified to be hydrophilic by coating with dextran. The dual-targeting peptides RGD10-NGR9 were conjugated to USPIO. Cell binding affinity and up-taking ability of the dual-targeting USPIO nanoparticles to integrin ανβ3-APN positive cells were subsequently tested by Prussian blue staining and phenanthroline colorimetry in vitro. The RGD10-NGR9 conjugated with USPIO was injected intravenously into xenograft mice, which were scanned by MRI at predetermined time points. The MRI and contrast-to-noise ratio (CNR) values were calculated to evaluate the ability of dual-targeting USPIO as a potential contrast agent in nude mice.
P-CLN-Dextran-USPIO nanoparticles with stable physical properties were successfully constructed. The average diameter of Fe3O4 nanoparticles was 8-10 nm, that of Dextran-USPIO was about 20 nm and P-CLN-Dextran-USPIO had an average diameter about 30 nm. The in vitro studies showed a better specificity of dual-targeting USPIO nanoparticles on proliferating human umbilical vein endothelia cells (HUVEC). In vivo, RGD10-NGR9-USPIO showed a significantly reduced contrast in signal intensity and 2.83-times increased the CNR in the tumor MRI in xenograft mice.
This novel synthesized RGD10-NGR9 dual-targeting USPIO is with better specific affinity in vitro and in vivo, and might be used as a molecular contrast agent for tumor angiogenesis MRI.
构建血管生成特异性RGD10-NGR9双靶向超顺磁性氧化铁纳米颗粒，评估其在裸鼠体内的磁共振成像（MRI）特征及在肿瘤MRI中的潜在诊断价值。
设计并合成双靶向肽RGD10-NGR9。采用化学共沉淀法合成超小超顺磁性氧化铁（USPIO）纳米颗粒，并用葡聚糖包被使其表面具有亲水性。将双靶向肽RGD10-NGR9偶联到USPIO上。随后通过普鲁士蓝染色和邻菲罗啉比色法在体外检测双靶向USPIO纳米颗粒对整合素ανβ3-氨肽酶N（APN）阳性细胞的细胞结合亲和力和摄取能力。将偶联有USPIO的RGD10-NGR9静脉注射到异种移植小鼠体内，在预定时间点进行MRI扫描。计算MRI和对比噪声比（CNR）值，以评估双靶向USPIO作为裸鼠潜在造影剂的能力。
成功构建了物理性质稳定的P-CLN-葡聚糖-USPIO纳米颗粒。Fe3O4纳米颗粒的平均直径为8-10nm，葡聚糖-USPIO的平均直径约为20nm，P-CLN-葡聚糖-USPIO的平均直径约为30nm。体外研究表明双靶向USPIO纳米颗粒对增殖的人脐静脉内皮细胞（HUVEC）具有更好的特异性。在体内，RGD10-NGR9-USPIO在异种移植小鼠的肿瘤MRI中显示信号强度对比度显著降低，CNR增加了2.83倍。
这种新合成的RGD10-NGR9双靶向USPIO在体外和体内均具有较好的特异性亲和力，可能用作肿瘤血管生成MRI的分子造影剂。
