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Folate-modified silicon carbide nanoparticles as multiphoton imaging nanoprobes for cancer-cell-specific labeling

机译:叶酸修饰的碳化硅纳米粒子作为多光子成像纳米探针,用于癌细胞特异性标记

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Interest in multiphoton microscopy for cell imaging has considerably increased over the last decade. Silicon carbide (SiC) nanoparticles exhibit strong second-harmonic generation (SHG) signal, and can thus be used as nonlinear optical probes for cell imaging. In this study, the surface of SiC nanoparticles was chemically modified to enable cancer-cell-specific labeling. In a first step, an aminosilane was grafted onto the surface of SiC nanoparticles. The resulting nanoparticles were further modified with folic acid, using an isothiocyanate-based coupling method. Nanoparticles from different functionalization steps were investigated by zeta potential measurement, colorimetric titration, infrared and ultraviolet-visible (UV-Vis) absorption spectroscopy, X-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Characterization results confirmed successful covalent grafting of silane and folic acid to nanoparticle surface. Finally, the efficacy of these folate-modified SiC nanoparticles for cancer-cell-specific labeling was evaluated by multiphoton microscopy, by measuring SHG-emitting cell area on multiphoton images. The average cancer-cell labeling percentage was about 48%, significantly higher than for negative controls (healthy cells, competition assay and poly(ethylene glycol) modified-SiC nanoparticles), where it ranged between 10% and 15%. These results demonstrated good efficiency and specificity for these folate-modified SiC nanoparticles in cancer-cell-specific labeling.
机译:在过去的十年中,对用于细胞成像的多光子显微镜的兴趣大大增加。碳化硅(SiC)纳米颗粒表现出很强的二次谐波生成(SHG)信号,因此可以用作细胞成像的非线性光学探针。在这项研究中,对SiC纳米颗粒的表面进行了化学修饰,以实现癌细胞特异性标记。第一步,将氨基硅烷接枝到SiC纳米颗粒的表面上。使用基于异硫氰酸酯的偶联方法,将得到的纳米颗粒进一步用叶酸改性。通过zeta电位测量,比色滴定,红外和紫外可见(UV-Vis)吸收光谱,X射线光电子能谱(XPS)和飞行时间二次离子质谱(ToF-模拟人生)。表征结果证实了硅烷和叶酸成功共价接枝到纳米颗粒表面。最后,通过测量多光子图像上发射SHG的细胞面积,通过多光子显微镜评估了这些叶酸修饰的SiC纳米颗粒对癌细胞特异性标记的功效。平均癌细胞标记百分比约为48%,明显高于阴性对照(健康细胞,竞争测定法和聚(乙二醇)修饰的SiC纳米颗粒)的百分比,其范围在10%至15%之间。这些结果证明了这些叶酸修饰的SiC纳米颗粒在癌细胞特异性标记中具有良好的效率和特异性。

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