Multivalent Self-Assembled DNA Polymer for Tumor-Targeted Delivery and Live Cell Imaging of Telomerase Activity

• Published in: Analytical chemistry (Washington) Vol. 90; no. 22; pp. 13188 - 13192
• Main Authors: Zhu, Xueli, Ye, Hongyan, Liu, Jin-Wen, Yu, Ru-Qin, Jiang, Jian-Hui
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20.11.2018
• Subjects: Aptamers; Aptamers, Nucleotide - chemistry; Aptamers, Nucleotide - genetics; Aptamers, Nucleotide - metabolism; Aptamers, Nucleotide - toxicity; Cancer; Carbocyanines - chemistry; Cell Line, Tumor; Cells; Cells (biology); Chemistry; Deoxyribonucleic acid; Diagnostic software; Diagnostic systems; DNA; DNA - chemistry; DNA - genetics; DNA - metabolism; DNA - toxicity; DNA polymerase; DNA probes; Enzyme Assays - methods; Fluorescence; Fluorescent Dyes - chemistry; Humans; Hybridization; Limit of Detection; Medical diagnosis; Medical imaging; Monitoring; Nucleic Acid Hybridization; Nucleolin; Nucleotide sequence; Phosphoproteins - metabolism; Polymers; Polymers - chemistry; Polymers - metabolism; Polymers - toxicity; RNA-Binding Proteins - metabolism; Self-assembly; Targeted cancer therapy; Telomerase; Telomerase - analysis; Tumor cells; Tumors
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/acs.analchem.8b04631

The efficient detection and in situ monitoring of telomerase activity is of great importance for cancer diagnosis and biomedical research. Here we report for the first time that the development of a novel multivalent self-assembled DNA polymer, constructed through telomerase primer sequence (ITS) triggered hybridization chain assembly using two functional hairpin probes (tumor-trageting aptamer modified H1 and signal probe modified H2), for sensitive detection and imaging of telomerase activity in living cells. After internalizing into the tumor cells by multivalent aptamer targeting, the ITS on DNA polymers can be elongated by intracellular telomerase to generate telomere repeat sequences that are complementary with the signal probe, which can proceed along the DNA polymers, and gradually light up the whole DNA polymers, leading to an enhanced fluorescence signal directly correlated with the activity of telomerase. Our results demonstrated that the developed DNA polymer show excellent performance for specifically detecting telomerase activity in cancer cells, dynamically monitoring the activity change of telomerase in response to telomerase-based drugs, and efficiently distinguishing cancer cells from normal cells. The proposed strategy may afford a valuable tool for the monitoring of telomerase activity in living cells and have great implications for biological and diagnostic applications.