构建及应用针对非小细胞肺癌整合素α_vβ_3受体靶向性纳米分子探针:体外实验研究  

Construction and application of integrin α_vβ_3 targeting nanocomposite for non-small cell lung cancer:In vitro study

作　　者：沈爱军[1,2] 张旭南[1] 李永勇 冯峰 张建泉[2] 王培军 SHEN Aijun;ZHANG Xu-nan;LI Yongyong;FENG Feng;ZHANG Jianquan;WANG Peijun(Department of Medical Imaging,Tongji Hospital,Tongji University,Shanghai 200065,China;Department of Medical Imaging,Nantong Tumor Hospital,Nantong University,Nantong 226361,China;The Institute for Biomedical Engineering&Nano Science,School of Medicine,Tongji University,Shanghai 200092,China)

机构地区：[1]同济大学附属同济医院影像科,上海200065 [2]南通大学附属肿瘤医院影像科,江苏南通226361 [3]同济大学医学院生物医学工程与纳米科学研究院,上海200092

出　　处：《中国医学影像技术》2018年第10期1445-1450,共6页Chinese Journal of Medical Imaging Technology

基　　金：国家自然科学基金面上项目(81470390);南通市科技局基金项目(MS12015100)

摘　　要：目的构建以整合素αvβ3为靶点的纳米分子探针,探讨其理化、生物学特征及对非小细胞肺癌A549细胞靶向性MR成像能力。方法构建以精氨酸-甘氨酸-天冬氨酸多肽(RGD)为靶向基团的分子探针RGD-Gd@BSA,检测其T1弛豫率、水合动力学直径、Zeta电位、分散稳定性和细胞毒性,并比较RGD-Gd@BSA(靶向组)和Gd@BSA(非靶向组)与肺癌A549细胞的靶向能力。结果线性拟合获得RGD-Gd@BSA的T1弛豫率为18.615L/(mmol·s),明显高于GdDTPA的3.404L/(mmol·s);RGD-Gd@BSA探针呈类球形,平均水合动力学直径为(99.52±2.62)nm;Zeta电位为(-11.07±0.42)mV,在溶液中分散稳定。Gd3+浓度为0.15、0.30、0.60、1.20和2.40μmol/L的RGD-Gd@BSA溶液中,人胚肾293T细胞的存活率分别为81.74%、86.80%、69.83%、78.41%和66.95%。共聚焦显微镜成像可见靶向组细胞具有比非靶向组更高的荧光强度;靶向组细胞悬液的T1WI相对信号强度高于非靶向组。结论纳米分子探针RGDGd@BSA具备稳定的理化特性、较好的生物相容性、较高的T1弛豫率和对肺癌A549细胞的靶向性,具有作为用于非小细胞肺癌特异性诊断的纳米分子探针的价值。Objective To synthesize integrinαvβ3 targeting nano-probe,and to observe its physicochemical characteristics,biological properties and the ability of targeting MRI imaging of non-small cell lung cancer(NSCLC)in vitro.Methods The peptide sequence Arg-Gly-Asp(RGD)targeted nano-probe(RGD-Gd@BSA)was prepared,then its longitudinal relaxivity rate,hydrodynamic diameter,Zeta potential,dispersion stability and cytotoxicity were tested.In addition,the targeting effect of A549 cells in vitro was compared between RGD-Gd@BSA(targeted group)and Gd@BSA(non-targeted group).Results T1 relaxivity rate of RGD-Gd@BSA was 18.615 L/(mmol·s)acquired from curve fitting method,significantly higher than that of Gd-DTPA 3.404 L/(mmol·s).The probe was round in shape,with the average hydrodynamic diameter of(99.52±2.62)nm and Zeta potential of(-11.07±0.42)mV.The dispersion stability of the probe was very well.When being incubated with RGD-Gd@BSA solutions with different Gd 3+concentrations(0.15,0.30,0.60,1.20 and 2.40μmol/L)for 24 h,the viability of human embryonic kidney 293T cells was 81.74%,86.80%,69.83%,78.41%and 66.95%,respectively.The fluorescence intensity in targeted group was higher than the non-targeted one,and T1WI signal intensity in targeted group was higher than that in non-targeted group.Conclusion RGD-Gd@BSA has stable physicochemical properties,favorable biocompatibility,high T1 relaxivity rate and good targeting ability to A549 Cell,being hopeful to efficient diagnosis of NSCLC.

关 键 词：整合素ΑVΒ3 钆 靶向性 磁共振成像 癌 非小细胞肺 

分 类 号：R734.2[医药卫生—肿瘤] R445.2[医药卫生—临床医学]