Near-infrared-traceable DNA nano-hydrolase: specific eradication of telomeric G-overhang in vivo
| Autor: | Xiaogang Qu, Yuhuan Sun, Hongshuang Qin, Jinsong Ren, Chuanqi Zhao, Jingsheng Niu, Tingting Cui |
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| Rok vydání: | 2020 |
| Předmět: |
AcademicSubjects/SCI00010
genetic processes Cell Antineoplastic Agents Biology 010402 general chemistry G-quadruplex 01 natural sciences Dexamethasone Mice 03 medical and health sciences chemistry.chemical_compound Complementary DNA Hydrolase Organometallic Compounds Genetics medicine Animals Humans 030304 developmental biology 0303 health sciences Hydrolysis Cerium Neoplasms Experimental Telomere 0104 chemical sciences Cell biology G-Quadruplexes enzymes and coenzymes (carbohydrates) Cell nucleus medicine.anatomical_structure chemistry Cancer cell MCF-7 Cells Nanoparticles Synthetic Biology and Bioengineering Cell aging DNA |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Telomeric DNA, whose length homeostasis is closely correlated with immortality of cancer cells, is regarded as a molecular clock for cellular lifespan. Regarding the capacity in forming G-quadruplex, G-rich 3′-overhang (G-overhang) has been considered as an attractive anticancer target. However, it is still challenging to precisely target telomeric G-overhang with current ligands because of the polymorphism of G-quadruplexes in cells. Herein, we construct a telomeric G-overhang-specific near-infrared-traceable DNA nano-hydrolase, which is composed of four parts: (i) dexamethasone for targeting cell nuclei; (ii) complementary DNA for hybridizing with G-overhang; (iii) multinuclear Ce(IV) complexes for hydrolyzing G-overhang; and (iv) upconversion nanoparticles for real-time tracking. The multivalent targeted DNA nano-hydrolase can be traced to precisely digest telomeric G-overhang, which contributes to telomeric DNA shortening and thereby causes cell aging and apoptosis. The anticancer treatment is further proved by in vivo studies. In this way, this design provides a telomeric G-overhang-specific eradication strategy based on a non-G-quadruplex targeting manner. |
| Databáze: | OpenAIRE |
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