Telomerase-Mediated Self-Assembly of DNA Network in Cancer Cells Enabling Mitochondrial Interference

Abstract

The precise control of the artificially induced reactions inside living cells is emerging as an effective strategy for the regulation of cell functions. Nevertheless, the manipulation of the assembly of exogenous molecules into artificial architectures in response to intracellular-specific signals remains a grand challenge. Herein, we achieve the precise self-assembly of deoxyribonucleic acid (DNA) network inside cancer cells, specifically responding to telomerase, and realize effective mitochondrial interference and the consequent regulation of cellular behaviors. Two functional DNA modules were designed: a mitochondria-targeting branched DNA and a telomerase-responsive linear DNA. Upon uptake by cancer cells, the telomerase primer in linear DNA responded to telomerase, and a strand displacement reaction was triggered by the reverse transcription of telomerase, thus releasing a linker DNA from the linear DNA. The linker DNA afterward hybridized with the branched DNA to form a DNA network on mitochondria. The DNA network interfered with the function of mitochondria, realizing the apoptosis of cancer cells. This system was further administered in a nude mouse tumor model, showing remarkable suppression of tumor growth. We envision that the telomerase-mediated intracellular self-assembly of the DNA network provides a promising route for cancer therapy.

Heavy Metal-Induced Assembly of DNA Network Biosensor from Double-Loop Hairpin Probes for Ultrasensitive Detection of UO22+ in Water and Soil Samples

“…Moreover, heavy metals can significantly reduce the catalytic activity of proteases. , Thus, there is an urgent need to develop an enzyme-free signal amplification approach for trace heavy metal detection in complex matrix samples. As an ideal alternative, signal amplification originating from DNA assembly can provide an enzyme-free format for target assay with high sensitivity. − With the advantages of high stability and flexibility, simple operation procedure, low cost, and convenient scalability, DNA assembly has been used in environmental monitoring and clinical diagnosis. − Exploring the construction of novel DNA assembly methods and applying them to the ultrasensitive detection of heavy metals is an interesting and challenging task.…”

Light-Driven Mitochondrion-to-Nucleus DNA Cascade Fluorescence Imaging and Enhanced Cancer Cell Photoablation

“…These nucleic acids undergo independent fission and fusion, which play a critical role in controlling mitochondrial replication, aging, and protein expression. − In the nucleus, nucleic acids encode, transmit, and express genetic information as they are the genetic material of life. − The nucleus is spatially separated from the cytosol, creating a distinct boundary between the mitochondrion and the nucleus. Because damage to nucleic acids in mitochondria and nuclei is closely associated with the mode of cell death, such as apoptosis, ferroptosis, and autophagy, certain anticancer drugs, such as doxorubicin, paclitaxel, carboplatin, and cisplatin, are designed to interact with nucleic acids to induce cell death. − Thus, detecting nucleic acids in the mitochondrion and nucleus in cascade mode is crucial for understanding diverse biological processes.…”

Dual-Stimuli Regulation of DNAzyme Cleavage Reaction by Coordination-Driven Nanoprobes for Cancer Cell Imaging

“…GSH and TE were selected as activators of interest due to their close relationship. First, the simultaneous elevation of both markers is more uniquely characteristic of cancer cells, associated with rapid tumor proliferation. , TE, a ribonucleoprotein enzyme that is commonly overexpressed in tumor cells, − leads to enhanced TE activity. This increase, in turn, causes the accumulation of oxidative stress, resulting in a significant surge in both the concentration and activity of GSH. − Second, employing only GSH might lead to false positives in conditions of oxidative stress in normal cells .…”