title: A cancer cell-activatable aptamer-reporter system for one-step assay of circulating tumor cells.
abstract: The current antibody-mediated numeration assays of circulating tumor cells (CTCs) require multiple steps and are time-consuming. To overcome these technical limitations, a cancer cell-activatable aptamer-reporter was formulated by conjugating a biomarker-specific aptamer sequence with paired fluorochrome-quencher molecules. In contrast to the antibody probes, the intact aptamer-reporter was optically silent in the absence of cells of interest. However, when used in an assay, the aptamer selectively targeted cancer cells through interaction with a specific surface biomarker, which triggered internalization of the aptamer-reporter and, subsequently, into cell lysosomes. Rapid lysosomal degradation of the aptamer-reporter resulted in separation of the paired fluorochrome-quencher molecules. The released fluorochrome emitted bright fluorescent signals exclusively within the targeted cancer cells, with no background noise in the assay. Thus, the assays could be completed in a single step within minutes. By using this one-step assay, CTCs in whole blood and marrow aspirate samples of patients with lymphoma tumors were selectively highlighted and rapidly detected with no off-target signals from background blood cells. The development of the cancer cell-activatable aptamer-reporter system allows for the possibility of a simple and robust point-of-care test for CTC detection, which is currently unavailable.
authors.affiliation: Department of Pathology and Genomic Medicine and Cancer Pathology Laboratory, Houston Methodist Hospital and Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Department of Translational Imaging, Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: Ching-Hsuan
authors.initials: CH
authors.lastname: Tung
authors.affiliation: Department of Pathology and Genomic Medicine and Cancer Pathology Laboratory, Houston Methodist Hospital and Houston Methodist Research Institute, Houston, Texas, USA.
authors.forename: Youli
authors.initials: Y
authors.lastname: Zu