Precision Spherical Nucleic Acids Enable Sensitive FEN1 Imaging and Controllable Drug Delivery for Cancer-Specific Therapy

Li, Shuang; Jiang, Qunying; Qing, Guangyan; Wang, Wenxiao; Yu, Wenjie; Wang, Fuan; Liu, Xiaoqing

doi:10.1021/acs.analchem.1c02264

Cited by 39 publications

(30 citation statements)

References 47 publications

(74 reference statements)

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“…The ingenious design of fluorescence sensing nanoplatforms shows immense importance for imaging intracellular biomarkers. − As the vital small molecule, adenosine triphosphate (ATP) plays an indispensable role in regulating many biochemical syntheses and metabolic processes in living entities. − A disordered ATP level is often associated with many biological processes or diseases such as Parkinson’s disease, hypoglycemia, hypoxia, ischemia, and angiocardiopathy. − Therefore, it is of essential significance to develop reliable and specific methods that can recognize and image ATP for biochemical research and clinical diagnosis.…”

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confidence: 99%

A Cooperatively Activatable DNA Nanoprobe for Cancer Cell-Selective Imaging of ATP

Zhou

Zou

et al. 2021

Anal. Chem.

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DNA-based nanoprobes have attracted extensive interest in the field of bioanalysis. Notably, engineered DNA nanoprobes that can respond to multiple pathological parameters are desirable to detect targets precisely. Here we design a split aptamer/DNAzyme (aptazyme)-based DNA probe for fluorescence detection of ATP and further develop a cooperatively activatable DNA nanoprobe for tumor-specific imaging of ATP in vivo. The DNA nanoprobes comprising split aptazyme-coated MnO 2 nanovectors have high stability and are synergistically activated by multiple biomarkers, GSH and ATP. Upon stimuli by overexpressed GSH in tumor cells, this DNA nanoprobe can release the aptazyme and self-supply cofactor Mn 2+ of the DNAzyme. Sequentially, intracellular ATP induces the proper folding of the split ATP aptamer and Mn 2+ -dependent DNAzyme, which activates the specific cleavage of substrate and generates the optical readout signal. This nanoprobe exhibits remarkable resistance to enzymatic degradation, satisfactory biosafety, identifies ATP specifically within cancer cells, and selectively lights up solid tumors. Our research provides a reliable method for ATP imaging in cancer cells and opens a new avenue for biochemical research and highly accurate disease diagnosis.

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confidence: 99%

A Cooperatively Activatable DNA Nanoprobe for Cancer Cell-Selective Imaging of ATP

Zhou

Zou

et al. 2021

Anal. Chem.

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“…Previous studies have indicated that FEN1 was overexpressed in multiple solid tumors like lung cancer and breast cancer with aggressive clinical implications 11 , 12 . In addition to its significance, in situ sensing of oncogenic FEN1 with DNA nanosphere or dumbbell DNA probe has been developed for early diagnosis and precision medicine 23 , 24 . Actually, a recent study noted that FEN1 expression was elevated in HCC tissues by analyzing bioinformatic data 25 .…”

Section: Discussionmentioning

confidence: 99%

Flap endonuclease 1 Facilitated Hepatocellular Carcinoma Progression by Enhancing USP7/MDM2-mediated P53 Inactivation

Bian¹,

Ni²,

Zhu³

et al. 2022

Int. J. Biol. Sci.

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Overexpression of Flap endonuclease 1 (FEN1) has been previously implicated in hepatocellular carcinoma (HCC), while its expression features and mechanisms remain unclear. In the current study, differential expression genes (DEGs) were screened in HCC tissues and normal liver tissues in 4 Gene Expression Omnibus (GEO) datasets. FEN1, one of the hub co-overexpressed genes, was further determined overexpressed in HCC tissues in TCGA, local HCC cohorts, and hepatocarcinogenesis model. In addition, high expression of FEN1 indicated poor prognosis of HCC patients. Loss-of-function and gain-of-function assays demonstrated that FEN1 enhanced the proliferation, cell cycle phage transition, migration/ invasion, therapy resistance, xenograft growth, and epithelial-mesenchymal transition (EMT) process of HCC cells. Mechanically, FEN1 could inactivate P53 signaling by preventing the ubiquitination and degradation of mouse double minute 2 (MDM2) via recruiting ubiquitin-specific protease 7 (USP7). Interfering USP7 with P22077 significantly reversed the malignant phenotypes activated by FEN1. In conclusion, this study suggests FEN1 as a robust prognostic biomarker and potential target for HCC.

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“…The BKM120-loaded DNA nanoparticles [ 86 ] can promote the apoptosis of lymphocytes in patients with primary CLL and serve as sensitizers for other anti-tumor drugs (such as Dox) without causing non-specific inflammation, and have a long circulation time (up to 24 h), systemic distribution, and accumulation at the tumor site. The Li team [ 87 ] has recently reported a DNA biosensor for the detection of flap endonuclease 1 (FEN1, one of the biomarkers of tumors) and in vivo and in vitro imaging. This DNA nanostructure has good stability, sensitivity, and specificity for FEN1 detection, and is expected to be used as a precise therapeutic agent for space-time controlled targeted drug administration.…”

Section: Dna Nanostructures For Drug Carriersmentioning

confidence: 99%

DNA Nanodevice-Based Drug Delivery Systems

2021

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DNA, a natural biological material, has become an ideal choice for biomedical applications, mainly owing to its good biocompatibility, ease of synthesis, modifiability, and especially programmability. In recent years, with the deepening of the understanding of the physical and chemical properties of DNA and the continuous advancement of DNA synthesis and modification technology, the biomedical applications based on DNA materials have been upgraded to version 2.0: through elaborate design and fabrication of smart-responsive DNA nanodevices, they can respond to external or internal physical or chemical stimuli so as to smartly perform certain specific functions. For tumor treatment, this advancement provides a new way to solve the problems of precise targeting, controllable release, and controllable elimination of drugs to a certain extent. Here, we review the progress of related fields over the past decade, and provide prospects for possible future development directions.

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Precision Spherical Nucleic Acids Enable Sensitive FEN1 Imaging and Controllable Drug Delivery for Cancer-Specific Therapy

Cited by 39 publications

References 47 publications

A Cooperatively Activatable DNA Nanoprobe for Cancer Cell-Selective Imaging of ATP

A Cooperatively Activatable DNA Nanoprobe for Cancer Cell-Selective Imaging of ATP

Flap endonuclease 1 Facilitated Hepatocellular Carcinoma Progression by Enhancing USP7/MDM2-mediated P53 Inactivation

DNA Nanodevice-Based Drug Delivery Systems

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