Multibranched Linear DNA-Controlled Assembly of Silver Nanoclusters and Their Applications in Aptamer-Based Cell Recognition

DNA-templated silver nanoclusters (DNA-AgNCs) are promising fluorescent materials and have been used in cancer diagnosis. Although many different DNA-AgNC applications have been realized, most of them rely on individual DNA-AgNCs or assembled DNA-AgNCs with limited recognition abilities, resulting in low detection sensitivity or off-target effects, in turn, hindering the performance of DNA-AgNCs in cancer cell recognition. As a solution, we assembled DNA-AgNCs by a multibranched linear (MBL) DNA structure formed through a trigger-initiated hybridization chain reaction (HCR) regarding the natural compatibility of DNA-AgNCs with DNA programmability and the advantages of DNA assembly in incorporating repetitive and functional moieties into one structure. By the specific modification of the trigger, MBL-AgNCs tethered with the targeting aptamer and partially hybridized duplex, which works as a component of DNA logic platform relying on the combination of cascade strand displacement reaction and specific recognition ability of aptamers, were obtained, respectively. DNA-AgNCs assembled by the aptamer-tethered MBL structure exhibited about 20-fold enhanced detection sensitivity in recognizing cancer cells compared to individual aptamer-tethered DNA-AgNCs. DNA-AgNCs assembled by the duplex-attached MBL exhibited logic performance in analyzing dual cell surface receptors with the assistance of "AND" logic platform, thus identifying cancer cells with high sensitivity and resolution. The facile conjugation of the MBL structure with different functional DNA structures makes it an ideal platform to assemble DNA-AgNCs used for aptamer-based cell recognition, thus broadening the potential applications of DNA-AgNCs.