The redox function of apurinic/apyrimidinic endonuclease 1 as key modulator in photodynamic therapy

Franchi, Leonardo Pereira; Lima, Jéssica Ellen Barbosa de Freitas; Piva, Henrique Luís; Tedesco, Antônio Cláudio

doi:10.1016/j.jphotobiol.2020.111992

Cited by 12 publications

(5 citation statements)

References 53 publications

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“…To test that our DNAzyme walker system is compatible with the complex sample matrix, we aimed to detect APE1 in cancer cell lysate. We chose to lyse and test HeLa cells for APE1 activity because HeLa cells are known to overexpress APE1 for enhanced chemoresistance. ,, Although APE1 is located primarily in the nucleus, overexpressed cytoplasmic APE1 is a hallmark factor of cancer cells. – After verifying the presence of APE1 in HeLa cell lysate with a Western blot (Figure S7), we successfully detected APE1 with our DNAzyme walker system (Figure ). Lysate originated from 10 6 cells was diluted serially in 100 μL of buffer to yield samples containing lysate of 1–50 cells.…”

Section: Resultsmentioning

confidence: 99%

“…We chose to lyse and test HeLa cells for APE1 activity because HeLa cells are known to overexpress APE1 for enhanced chemoresistance. 30 , 38 , 39 Although APE1 is located primarily in the nucleus, overexpressed cytoplasmic APE1 is a hallmark factor of cancer cells. 40 – 43 After verifying the presence of APE1 in HeLa cell lysate with a Western blot ( Figure S7 ), we successfully detected APE1 with our DNAzyme walker system ( Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

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Development of a DNAzyme Walker for the Detection of APE1 in Living Cancer Cells

Tao,

Zhang,

Weinfeld

et al. 2023

Anal. Chem.

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DNAzyme walker technology is a compelling option for bioanalytical and drug delivery applications. While nucleic acid and protein targets have been used to activate DNAzyme walkers, investigations into enzyme-triggered DNAzyme walkers in living cells are still in their early stages. The base excision repair (BER) pathway presents an array of enzymes that are overexpressed in cancer cells. Here, we introduce a DNAzyme walker system that sensitively and specifically detects the BER enzyme apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1). We constructed the DNAzyme walker on the surface of 20 nm-diameter gold nanoparticles. We achieved a detection limit of 160 fM of APE1 in a buffer and in whole cell lysate equivalent to the amount of APE1 in a single HeLa cell in a sample volume of 100 μL. Confocal imaging of the DNAzyme walking reveals a cytoplasmic distribution of APE1 in HeLa cells. Walking activity is tunable to exogenous Mn2+ concentrations and the uptake of the DNAzyme walker system does not require transfection assistance. We demonstrate the investigative potential of the DNAzyme walker for up-regulated or overactive enzyme biomarkers of the BER pathway in cancer cells.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Development of a DNAzyme Walker for the Detection of APE1 in Living Cancer Cells

Tao,

Zhang,

Weinfeld

et al. 2023

Anal. Chem.

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“…In this proof-of-concept study, we selected human apurinic/ apyrimidinic endonuclease 1 (APE1), an important enzyme distributed in various subcellular compartments and involved in several physiological processes such as DNA base excision repair and redox signaling, [53][54][55][56] as the model enzyme. As shown in Figure 4a, the UV light-activatable, APE1-sensing DNA probe (namely APÀ P) was constructed by annealing the AP-strand and P-strand, which contains an apurinic/apyrimidinic (AP) site and a photocleavable (PC) linker, respectively.…”

Section: Dna Serves As a Sensing Unit For Imaging Of Subcellular Enzy...mentioning

confidence: 99%

“…[60,61] It was reported that APE1 possesses an anti-apoptotic function and its subcellular distribution can impact therapeutic outcome of PDT. [55,56] To elucidate the action mechanism of APE1's influence during this therapeutic process, we recently presented a multifunctional nanoplatform that is capable of monitoring subcellular dynamics of APE1 during the NIR lighttriggered, mitochondria-targeted PDT. [42] As shown in Figure 6, this highly modular nanoplatform (termed UR-HAPT) consists of four distinctive components: 1) a Yb/Er co-doped UCNP serving as both a light transducer and a delivery scaffold; 2) rose bengal (RB) as PSs for PDT; 3) TPP for mitochondria targeting; and 4) a DNA probe (denoted as HAP) for imaging APE1's activity.…”

Section: Dna Serves As a Sensing Unit For Imaging Of Subcellular Enzy...mentioning

confidence: 99%

“…It was reported that APE1 possesses an anti‐apoptotic function and its subcellular distribution can impact therapeutic outcome of PDT [55,56] . To elucidate the action mechanism of APE1’s influence during this therapeutic process, we recently presented a multifunctional nanoplatform that is capable of monitoring subcellular dynamics of APE1 during the NIR light‐triggered, mitochondria‐targeted PDT [42] .…”

Section: Dna Serves As a Sensing Unit For Imaging Of Subcellular Enzy...mentioning

confidence: 99%

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DNA‐Based Biosensors for Imaging of Subcellular Enzymatic Activity

Zhao

et al. 2022

Analysis & Sensing

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As one kind of the most important biomolecules, enzymes participate in nearly all biochemical reactions. Dysregulation of enzymes' spatial distributions and activities is often associated with many diseases. In situ imaging of enzymatic activity at the subcellular level is extremely challenging due to the lack of spatiotemporal precision of sensor probes. In this concept, we introduce several recent works in which DNA-based biosensors with controllable localization ability were constructed for imaging of specific enzymatic activities and dynamics in a subcellular compartment of interest. These DNA-based biosensors are classified into two types, in which DNA molecules serve as a subcellular targeting scaffold and an enzyme responsive sensing unit, respectively. We highlight the working principles of these DNA-based biosensors and briefly introduce their biological applications. Finally, we discuss current limitations and future opportunities in this emerging field.

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Spatially Selective Monitoring of Subcellular Enzyme Dynamics in Response to Mitochondria‐Targeted Photodynamic Therapy

Shao

Chai

et al. 2022

Angewandte Chemie

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Tracking spatial and temporal dynamics of bioactive molecules such as enzymes responding to therapeutic treatment is highly important for understanding of the related functions. However, in situ molecular imaging at subcellular level during photodynamic therapy (PDT) has been hampered by the limitations of existing methods. Herein, we present a multifunctional nanoplatform (termed as UR-HAPT) that is able to simultaneously monitor subcellular dynamics of human apurinic/apyrimidinic endonuclease 1 (APE1) during the near-infrared (NIR) light-mediated PDT. UR-HAPT was constructed by the combination of an upconversion nanoparticle-based PDT design and a mitochondria-targeting strategy with an APE1-responsive DNA reporter. Benefiting from the gain-of-function approach, activatable mitochondrial accumulation of APE1 in response to the oxidative stress was observed during the NIR light-triggered, mitochondria-targeted PDT process. We envision that this nanoplatform can be applicable to screen and evaluate potential enzyme inhibitors to improve the PDT efficacy.

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The redox function of apurinic/apyrimidinic endonuclease 1 as key modulator in photodynamic therapy

Cited by 12 publications

References 53 publications

Development of a DNAzyme Walker for the Detection of APE1 in Living Cancer Cells

Development of a DNAzyme Walker for the Detection of APE1 in Living Cancer Cells

DNA‐Based Biosensors for Imaging of Subcellular Enzymatic Activity

Spatially Selective Monitoring of Subcellular Enzyme Dynamics in Response to Mitochondria‐Targeted Photodynamic Therapy

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