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内切酶响应适体功能化水凝胶涂层用于癌细胞的顺序捕获和释放。

Endonuclease-responsive aptamer-functionalized hydrogel coating for sequential catch and release of cancer cells.

机构信息

Program of Biomedical Engineering, School of Engineering, University of Connecticut, Storrs, CT 06269-3222, USA.

出版信息

Biomaterials. 2013 Jan;34(2):460-9. doi: 10.1016/j.biomaterials.2012.09.040. Epub 2012 Oct 17.

Abstract

Rare circulating tumor cells are a promising biomarker for the detection, diagnosis, and monitoring of cancer. However, it remains a challenge to develop biomedical devices for specific catch and nondestructive release of circulating tumor cells. The purpose of this study was to explore a unique system for cell catch and release by using aptamer-functionalized hydrogels and restriction endonucleases. The results show that the hydrogel coating was highly resistant to nonspecific cell binding with ~5-15 cells/mm(2) on the hydrogel surface. In contrast, under the same condition, the aptamer-functionalized hydrogel coating could catch target cancer cells with a density over 1000 cells/mm(2). When the hydrogel coating was further treated with the restriction endonucleases, the bound cells were released from the hydrogel coating because of the endonuclease-mediated sequence-specific hydrolysis of the aptamer sequences. The release efficiency reached ~99%. Importantly, ~98% of the released cells maintained viability. Taken together, this study demonstrates that it is promising to apply endonuclease-responsive aptamer-functionalized hydrogels as a coating material to develop medical devices for specific catch and nondestructive release of rare circulating tumor cells.

摘要

稀有循环肿瘤细胞是一种很有前途的生物标志物,可用于癌症的检测、诊断和监测。然而,开发用于特定捕获和无损释放循环肿瘤细胞的生物医学设备仍然是一个挑战。本研究旨在探索一种独特的系统,通过使用适配体功能化水凝胶和限制内切酶来实现细胞的捕获和释放。结果表明,水凝胶涂层具有高度抵抗非特异性细胞结合的能力,在水凝胶表面的细胞密度约为 5-15 个/mm(2)。相比之下,在相同条件下,适配体功能化水凝胶涂层可以捕获目标癌细胞,其密度超过 1000 个细胞/mm(2)。当水凝胶涂层进一步用限制内切酶处理时,由于内切酶介导的适配体序列的序列特异性水解,结合的细胞从水凝胶涂层中释放出来。释放效率达到约 99%。重要的是,约 98%的释放细胞保持活力。总之,这项研究表明,将内切酶响应的适配体功能化水凝胶作为涂层材料应用于开发用于稀有循环肿瘤细胞的特定捕获和无损释放的医疗设备是很有前途的。

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