CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China.
CAS Key Laboratory for Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China; The Second Affiliated Hospital of Soochow University, Suzhou, 215008, China.
Colloids Surf B Biointerfaces. 2021 Jun;202:111669. doi: 10.1016/j.colsurfb.2021.111669. Epub 2021 Mar 2.
The detection and analysis of circulating tumor cells (CTCs) from cancer patients' blood samples present a powerful means to monitor cancer progression. In this work, an antifouling nanostructure substrate made of hydrogel nanoparticles was fabricated for an effective capture of CTCs from the blood samples. The hydrogel nanoparticles were synthesized by zwitterionic sulfobetaine methacrylate (SBMA), methacrylic acid (MAA) and N, N'-methylene bisacrylamide (MBA) through a simple polymerization. SBMA could provide an effective antifouling layer for the substrate to prevent nonspecific cell adhesion, MAA could afford active carboxyl groups for the immobilization of antibody to achieve specific CTC capture, and the nanostructured surface could improve the interaction of the target cells with the antibody modified substrate surface to enhance the capture efficiency of CTCs. Moreover, it was not necessary to further modify the antifouling molecules on the hydrogel nanoparticle substrate's surface, reducing the complexity and difficulty of the substrate preparation. The results showed that about 87 % of target cells (MCF-7 cells) were captured on the antibody modified hydrogel nanoparticle substrate. In contrast, the substrate showed little adhesive capacity for the nonspecific cells (K562 cells), and only 0.15 % of cells were captured. And 98 % of the captured cells kept good cell viability. Finally, 1-32 CTCs/mL were detected from the blood samples of five cancer patients, while no CTC was found in five healthy samples. It is envisaged that the new hydrogel nanostructure substrate is capable of capturing CTCs efficiently and specifically from patient blood samples to be used in cancer treatment.
从癌症患者的血液样本中检测和分析循环肿瘤细胞(CTC)提供了一种监测癌症进展的强大手段。在这项工作中,制备了一种由水凝胶纳米粒子组成的抗污纳米结构基底,用于从血液样本中有效捕获 CTC。水凝胶纳米粒子通过两性离子磺基甜菜碱甲基丙烯酰胺(SBMA)、甲基丙烯酸(MAA)和 N,N'-亚甲基双丙烯酰胺(MBA)的简单聚合合成。SBMA 可为基底提供有效的抗污层,以防止非特异性细胞黏附,MAA 可为抗体的固定提供活性羧基基团,以实现特定的 CTC 捕获,纳米结构化表面可以改善靶细胞与抗体修饰基底表面的相互作用,从而提高 CTC 的捕获效率。此外,无需进一步修饰水凝胶纳米粒子基底表面上的抗污分子,降低了基底制备的复杂性和难度。结果表明,约 87%的靶细胞(MCF-7 细胞)被抗体修饰的水凝胶纳米粒子基底捕获。相比之下,该基底对非特异性细胞(K562 细胞)的黏附能力很小,仅捕获了 0.15%的细胞。并且 98%的捕获细胞保持良好的细胞活力。最后,从五名癌症患者的血液样本中检测到 1-32 个 CTCs/mL,而在五名健康样本中未发现 CTC。可以预见,这种新的水凝胶纳米结构基底能够从患者的血液样本中高效且特异性地捕获 CTC,用于癌症治疗。