DNA Hydrogel with Aptamer-Toehold-Based Recognition, Cloaking, and Decloaking of Circulating Tumor Cells for Live Cell Analysis

Circulating tumor
cells (CTCs) contain molecular information on
the primary tumor and can be used for predictive cancer diagnostics.
Capturing rare live CTCs and their quantification in whole blood remain
technically challenging. Here we report an aptamer-trigger clamped
hybridization chain reaction (atcHCR) method for in situ identification
and subsequent cloaking/decloaking of CTCs by porous DNA hydrogels.
These decloaked CTCs were then used for live cell analysis. In our
design, a DNA staple strand with aptamer-toehold biblocks specifically
recognizes epithelial cell adhesion molecule (EpCAM) on the CTC surface
that triggers subsequent atcHCR via toehold-initiated branch migration.
Porous DNA hydrogel based-cloaking of single/cluster of CTCs allows
capturing of living CTCs directly with minimal cell damage. The ability
to identify a low number of CTCs in whole blood by DNA hydrogel cloaking
would allow high sensitivity and specificity for diagnosis in clinically
relevant settings. More significantly, decloaking of CTCs using controlled
and defined chemical stimuli can release living CTCs without damages
for subsequent culture and live cell analysis. We expect this liquid
biopsy tool to open new powerful and effective routes for cancer diagnostics
and therapeutics.