Multivalence Aptamers Enhance Transmembrane Efficiency of Localized Catalytic Hairpin Assembly-Based Nanomachine for Sensitive Cell Imaging.

As a promising scaffold material, DNA tetrahedrons (TDNs) were integrated with localized catalytic hairpin assembly (LCHA) to develop a nanomachine. However, the TDN nanomachine, as an exogenous material, has difficulty directly penetrating the membrane, posing a bottleneck for cell imaging. To address this issue, multivalent aptamers were assembled on an LCHA-based TDN nanomachine. Within the DNA nanomachine, TDN precisely modulated the valency of the aptamer, thereby affecting the affinity for the membrane protein. In the in vitro experiments, aptamer valency on the TDN nanomachine did not affect the sensing performance for miRNA-21 detection. The cell imaging experiments showed a significant phenomenon that aptamer valence-dependent fluorescent signal enhancement was observed on the MUC1-overexpressed cell lines rather than the MUC1-low-expressed cell lines. The reason why the TDN nanomachine functionalized with a multivalent aptamer enhanced the transmembrane efficiency is that multivalent aptamers with high local concentrations increase the affinity for the cell membrane. Highly sensitive miR-21 detection in the cancer cells was achieved using a TDN nanomachine modified with trivalent aptamers. Owing to their high transmembrane efficiency and sensitive cell imaging capability, TDN nanomachines with multivalence aptamers are expected to become a novel tool for cancer diagnostics.