Journal
NUCLEIC ACIDS RESEARCH
Volume 48, Issue 17, Pages 9986-9994Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkaa693
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Funding
- National Natural Science Foundation of China [21533008, 21820102009, 21871249, 91856205, 21202158]
- Key Research Program of Frontier Sciences of the Chinese Academy of Sciences [QYZDJ-SSW-SLH052]
- National Natural Science Foundation of China
- Key Research Program of Frontier Sciences of the Chinese Academy of Sciences
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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 nearinfrared-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.
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