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学者姓名：卞懿洁
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Abstract ：
Telomerase has long been considered as a biomarker for cancer diagnosis and a therapeutic target for drug discovery. Detecting telomerase activity in vivo could provide more direct information of tumor progression and response to drug treatment, which, however, is hampered by the lack of an effective probe that can generate an output signal without a tissue penetration depth limit. In this study, using the principle of distance-dependent magnetic resonance tuning, we constructed a telomerase-activated magnetic resonance imaging probe (TAMP) by connecting superparamagnetic ferroferric oxide nanoparticles (SPFONs) and paramagnetic Gd-DOTA (Gd(III) 1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraazacyclododecane-1,4,7,10-tet-raacetic acid) complexes via telomerase-responsive DNA motifs. Upon telomerase-catalyzed extension of the primer in TAMP, Gd-DOTA-conjugated oligonucleotides can be liberated from the surface of SPFONs through a DNA strand displacement reaction, restoring the T1 signal of the Gd-DOTA for a direct readout of the telomerase activity. Here we show that, by tracking telomerase activity, this probe provides consistent monitoring of tumor growth kinetics during progression and in response to drug treatment and enables in situ screening of telomerase inhibitors in whole-animal models. This study provides an alternative toolkit for cancer diagnosis, treatment response assessment, and anticancer drug screening.
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| GB/T 7714 | Dai, Junduan , Liu, Zheng , Wang, Lili et al. A Telomerase-Activated Magnetic Resonance Imaging Probe for Consecutively Monitoring Tumor Growth Kinetics and In Situ Screening Inhibitors [J]. | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 2023 , 145 (2) : 1108-1117 . |
| MLA | Dai, Junduan et al. "A Telomerase-Activated Magnetic Resonance Imaging Probe for Consecutively Monitoring Tumor Growth Kinetics and In Situ Screening Inhibitors" . | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 145 . 2 (2023) : 1108-1117 . |
| APA | Dai, Junduan , Liu, Zheng , Wang, Lili , Huang, Guoming , Song, Sijie , Chen, Chen et al. A Telomerase-Activated Magnetic Resonance Imaging Probe for Consecutively Monitoring Tumor Growth Kinetics and In Situ Screening Inhibitors . | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY , 2023 , 145 (2) , 1108-1117 . |
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Abstract ：
The toxicity and complicated administration procedures of transition metal catalysts have hampered the applications of bioorthogonal catalysis in vivo. Here the authors fill the needles of a microneedle array patch with palladium nanoparticles deposited on titanium nanosheets and show that the device, applied locally on the skin of mouse models bearing melanoma, promotes intratumoural conversion of systemically injected caged doxorubicin into the active drug, reducing its toxicity and side effects. Bioorthogonal catalysis mediated by transition metals has inspired a new subfield of artificial chemistry complementary to enzymatic reactions, enabling the selective labelling of biomolecules or in situ synthesis of bioactive agents via non-natural processes. However, the effective deployment of bioorthogonal catalysis in vivo remains challenging, mired by the safety concerns of metal toxicity or complicated procedures to administer catalysts. Here, we describe a bioorthogonal catalytic device comprising a microneedle array patch integrated with Pd nanoparticles deposited on TiO2 nanosheets. This device is robust and removable, and can mediate the local conversion of caged substrates into their active states in high-level living systems. In particular, we show that such a patch can promote the activation of a prodrug at subcutaneous tumour sites, restoring its parent drug's therapeutic anticancer properties. This in situ applied device potentiates local treatment efficacy and eliminates off-target prodrug activation and dose-dependent side effects in healthy organs or distant tissues.
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| GB/T 7714 | Chen, Zhaowei , Li, Hongjun , Bian, Yijie et al. Bioorthogonal catalytic patch [J]. | NATURE NANOTECHNOLOGY , 2021 , 16 (8) : 933-, . |
| MLA | Chen, Zhaowei et al. "Bioorthogonal catalytic patch" . | NATURE NANOTECHNOLOGY 16 . 8 (2021) : 933-, . |
| APA | Chen, Zhaowei , Li, Hongjun , Bian, Yijie , Wang, Zejun , Chen, Guojun , Zhang, Xudong et al. Bioorthogonal catalytic patch . | NATURE NANOTECHNOLOGY , 2021 , 16 (8) , 933-, . |
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