A Multivariate‐Gated DNA Nanodevice for Spatioselective Imaging of Pro‐metastatic Targets in Extracellular Microenvironment

Xiang, Zhichu; Zhao, Jian; Qu, Junle; Song, Jun; Li, Lele

doi:10.1002/anie.202111836

Cited by 35 publications

(22 citation statements)

References 44 publications

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“…An TME consists of a complex network of tumor cells within an extremely complex internal environment formed by tumor stromal cells and their secreted active factors, as well as vascular and lymphatic networks, and extracellular matrix ( Xiang et al, 2022 ), of which immune cells and stromal cells were the most common non-tumor cells in TME.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel immune ferroptosis-related genes associated with clinical and prognostic features in breast cancer

Xie

Liu

et al. 2023

Front. Genet.

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Introduction: Breast cancer is the most common form of cancer among women, it is critical to identify potential targets and prognostic biomarkers. Ferroptosis combined with immunity shows a pivotal role in a variety of tumors, which provides new opportunities to detect and treat breast cancer.Methods: Our first step was to combine multiple datasets to search for immune ferroptosis-related mRNAs. In the next step, risk signatures were created using Least Absolute Shrinkage and Selection Operator (LASSO). After that, based on the results of the multivariate Cox analysis, we created a prognostic nomogram and validated the model’s accuracy. Finally, functional enrichment analysis, single sample gene set enrichment analysis (ssGSEA), immunity and drug sensitivity correlation analysis were performed to explore the possible mechanisms by which these immune ferroptosis associated mRNAs affect BRCA survival.Results: An immune ferroptosis signature (IFRSig) consisting of 5 mRNAs was constructed and showed excellent predictability in the training and validation cohorts. A correlation analysis revealed that clinical characteristics were closely related to risk characteristics. Our nomogram model, which we created by combining risk characteristics and clinical parameters, was proven to be accurate at predicting BRCA prognosis. Further, we divided patients into lowrisk and high-risk groups based on the expression of the model-related genes. Compared with low-risk group, high-risk group showed lower levels of immune cell infiltration, immune-related functions, and immune checkpoints molecules, which may associate with the poor prognosis.Discussion: The IFRSig could be used to predict overall survival (OS) and treatment response in BRCA patients and could be viewed as an independent prognostic factor. The findings in this study shed light on the role of immune ferroptosis in the progression of BRCA.

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Section: Discussionmentioning

confidence: 99%

Identification of novel immune ferroptosis-related genes associated with clinical and prognostic features in breast cancer

Xie

Liu

et al. 2023

Front. Genet.

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Section: Enzyme-triggered Aptamer Sensors For Cell-selective Imaging ...mentioning

confidence: 99%

Enzyme-Triggered DNA Sensor Technology for Spatially-Controlled, Cell-Selective Molecular Imaging

2023

Acc. Chem. Res.

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Conspectus With unparalleled programmability, DNA has evolved as a powerful scaffold for engineering intricate and dynamic systems that can perform diverse tasks. By allowing serial detection of molecular targets in complex cellular milieus, increasingly sophisticated DNA sensors have not only promoted significant advances in unveiling the fundamental mechanisms of various pathophysiological processes but also provided a useful toolkit for disease diagnostics based on molecular signatures. Despite much progress, an inherent limitation of DNA-based sensors is that they often lack spatial control and cell-type selectivity for the sensing activity because of their “always active” design mechanism. Since most molecular targets of interests are not exclusive to disease cells, they are also shared by normal cells, the application of such biosensors for disease-specific imaging is limited by inadequate signal-to-background ratios due to indistinguishable signal response in both disease and normal cells. Therefore, imparting biosensors with spatial controllability remains a key issue to achieve molecular imaging with high sensitivity and cell specificity. As a biocatalyst, enzyme has been found to be closely related with the pathological conditions of numerous diseases. For example, many nucleases, protease, and kinases have been identified overexpressed in disease cells and considered as important biomarkers of cancer, inflammation, and neurological diseases. Recently, we have envisioned that such pathophysiology-associated enzymes could be leveraged as endogenous triggers to achieve spatial control over the molecular imaging activity of the DNA-based sensors with improved cell-specificity. In this Account, we outline the research efforts from our group on the development of endogenous enzyme-triggered, DNA-based sensor technology that enables spatially controlled, cell-type selective molecular imaging. With programmable DNA design and further engineering of enzymatically cleavable sites, a series of DNAzyme- and aptamer-based sensors have been developed for enzyme-controlled imaging of various molecular targets (e.g., metal ions and small molecules) in a cancer cell-selective manner. In particular, by introduction of PNA as bridge molecules to engineer DNA-based sensors with functional peptides, the conceptual design of protease-activated DNA biosensors has been established for spatioselective molecular imaging in cancer cells and extracellular tumor microenvironments. Furthermore, enzyme-triggered signal amplification approaches, such as enzymatically activated molecular beacon and catalytic hairpin assembly, have been developed for spatially selective RNA imaging in specific disease cells (e.g., inflammatory cells and cancer cells), which enables enhanced disease-site specificity and thus improved signal-to-background ratio. The signal amplification strategy is further expanded to cell-selective amplified imaging of non-RNA species through the combination with functional DNA design. Finally, the challenges and potent...

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“…These small molecules-responsive DNA nanocarriers provide a new perspective for the design of tumor diagnosis and therapy strategies. 42–44 …”

Section: Major Stimuli-responsive Dna Systems In Ddnsmentioning

confidence: 99%

Advances and prospects of dynamic DNA nanostructures in biomedical applications

Chen

Shi

2022

RSC Adv.

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A Multivariate‐Gated DNA Nanodevice for Spatioselective Imaging of Pro‐metastatic Targets in Extracellular Microenvironment

Cited by 35 publications

References 44 publications

Identification of novel immune ferroptosis-related genes associated with clinical and prognostic features in breast cancer

Identification of novel immune ferroptosis-related genes associated with clinical and prognostic features in breast cancer

Enzyme-Triggered DNA Sensor Technology for Spatially-Controlled, Cell-Selective Molecular Imaging

Advances and prospects of dynamic DNA nanostructures in biomedical applications

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