| 沈爱军,张旭南,李永勇,冯峰,张建泉,王培军.构建及应用针对非小细胞肺癌整合素αvβ3受体靶向性纳米分子探针:体外实验研究[J].中国医学影像技术,2018,34(10):1445~1450 |
| 构建及应用针对非小细胞肺癌整合素αvβ3受体靶向性纳米分子探针:体外实验研究 |
| Construction and application of integrin αvβ3 targeting nanocomposite for non-small cell lung cancer: In vitro study |
| 投稿时间：2018-03-07 修订日期：2018-06-20 |
| DOI：10.13929/j.1003-3289.201803041 |
| 中文关键词: 整合素αvβ3 钆 靶向性 磁共振成像 癌,非小细胞肺 |
| 英文关键词:Integrin αvβ3 Gadolinium Target Magnetic resonance imaging Carcinoma,non-small-cell lung |
| 基金项目:国家自然科学基金面上项目（81470390）、南通市科技局基金项目（MS12015100）。 |
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| 中文摘要: |
| 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18.615 L/（mmol·s），明显高于Gd-DTPA的3.404 L/（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2.40 μmol/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RGD-Gd@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。 |
| 英文摘要: |
| Objective To synthesize integrin αvβ3 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 Gd3+ concentrations (0.15, 0.30, 0.60, 1.20 and 2.40 μmol/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. |
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