We present here a pH-responsive activatable aptamer probe for targeted cancer imaging based on i-motif-driven conformation alteration. This pH-responsive activatable aptamer probe is composed of two single-stranded DN...We present here a pH-responsive activatable aptamer probe for targeted cancer imaging based on i-motif-driven conformation alteration. This pH-responsive activatable aptamer probe is composed of two single-stranded DNA. One was used for target recognition, containing a central, target specific aptamer sequence at the 3'-end and an extension sequence at the 5'-end with 5-carboxytetramethylrhodamine (TAMRA) label (denoted as strand A). The other (strand |), being competent to work on the formation of i-motif structure, contained four stretches of the cytosine (C) rich domain and was labeled with a Black Hole Quencher 2 (BHQ2) at the 3'-end. At neutral or slightly alkaline pH, strand | was hybridized to the extension sequence of strand A to form a double-stranded DNA probe, termed i-motif-based activatable aptamer probe (I-AAP). Because of proximity- induced energy transfer, the I-AAP was in a "signal off' state. The slightly acidic pH enforced the strand I to form an intramo- lecular i-motif and then initiated the dehybridization of I-AAP, leading to fluorescence readout in the target recognition. As a demonstration, AS1411 aptamer was used for MCF-7 cells imaging. It was displayed that the I-AAP could be carried out for target cancer cells imaging after being activated in slightly acidic environment. The applicability of I-AAP for tumor tissues imaging has been also investigated by using the isolated MCF-7 tumor tissues. These results implied the I-AAP strategy is promising as a novel approach for cancer imaging.展开更多
基金supported by the Key Project of National Natural Science Foundation of China (21175039, 21322509, 21305035, 21190044, 21221003, 21305038, 2015JJ3044)
文摘We present here a pH-responsive activatable aptamer probe for targeted cancer imaging based on i-motif-driven conformation alteration. This pH-responsive activatable aptamer probe is composed of two single-stranded DNA. One was used for target recognition, containing a central, target specific aptamer sequence at the 3'-end and an extension sequence at the 5'-end with 5-carboxytetramethylrhodamine (TAMRA) label (denoted as strand A). The other (strand |), being competent to work on the formation of i-motif structure, contained four stretches of the cytosine (C) rich domain and was labeled with a Black Hole Quencher 2 (BHQ2) at the 3'-end. At neutral or slightly alkaline pH, strand | was hybridized to the extension sequence of strand A to form a double-stranded DNA probe, termed i-motif-based activatable aptamer probe (I-AAP). Because of proximity- induced energy transfer, the I-AAP was in a "signal off' state. The slightly acidic pH enforced the strand I to form an intramo- lecular i-motif and then initiated the dehybridization of I-AAP, leading to fluorescence readout in the target recognition. As a demonstration, AS1411 aptamer was used for MCF-7 cells imaging. It was displayed that the I-AAP could be carried out for target cancer cells imaging after being activated in slightly acidic environment. The applicability of I-AAP for tumor tissues imaging has been also investigated by using the isolated MCF-7 tumor tissues. These results implied the I-AAP strategy is promising as a novel approach for cancer imaging.