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

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/mm² 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/mm². 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.