Mitochondria-Targeted DNA-Based Nanoprobe for In Situ Monitoring of the Activity of the mtDNA Repair Enzyme and Evaluating Tumor Radiosensitivity

Analytical Chemistry, Journal Year: 2025, Volume and Issue: 97(1), P. 382 - 391

Published: Jan. 2, 2025

Evaluating tumor radiosensitivity is beneficial for the prediction of treatment efficacy, customization plans, and minimization side effects. Tracking mitochondrial DNA (mtDNA) repair process helps to assess as mtDNA determines fate cell under radiation-induced damage. However, current probes developed monitor levels enzymes suffered from complex synthesis, uncontrollable preparation, limited selectivity, poor organelle-targeting ability. Especially, correlation between activity inherent tumors has not yet been explored. Here, we present a mitochondria-targeted DNA-based nanoprobe (TPP-Apt-tFNA) in situ monitoring enzyme evaluating radiosensitivity. TPP-Apt-tFNA consists tetrahedral framework precisely modified with three functional modules on each vertexes, that is, cell-targeting aptamer, mitochondrion-targeting moiety, apurinic/apyrimidinic endonuclease 1 (APE1)-responsive molecule beacon. Once selectively internalized by cells, targeted mitochondrion specifically recognized APE1 activate fluorescence, allowing observation activity. The showed elevated mitochondria cells oxidative stress. Moreover, enabled illumination different APE1-mediated cycle phases. Furthermore, using vitro vivo, found high repair, which allowed them recover lesions, had low sensitivity radiation an unsatisfactory radiotherapy outcome. Our work provides new imaging tool exploring roles diverse biological processes guiding treatment.

Language: Английский

Subcellular Compartment‐Specific Amplified Imaging of Metal Ions via Ribosomal RNA‐Regulated DNAzyme Sensors

Angewandte Chemie, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 31, 2024

Abstract Although DNAzyme sensors have been widely developed for imaging metal ions, their application in specific subcellular compartments remains challenging due to low spatial controllability. Here we present a locally activatable, DNAzyme‐based sensing technology that enables compartment‐specific of ions through ribosomal RNA (rRNA) regulated signal amplification. The system leverages subcellularly encoded rRNA activate sensors, and further drives amplification via multiple turnover cleavage molecular beacons, significantly enhance sensitivity precision metal‐ion organelles (e.g. mitochondria) or membraneless cytosol). Furthermore, demonstrate the allows situ monitoring dynamics mitochondrial Zn 2+ during ischemia drug intervention. This study expands toolbox investigating role disease processes.

Language: Английский

Subcellular Compartment‐Specific Amplified Imaging of Metal Ions via Ribosomal RNA‐Regulated DNAzyme Sensors

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 31, 2024

Although DNAzyme sensors have been widely developed for imaging metal ions, their application in specific subcellular compartments remains challenging due to low spatial controllability. Here we present a locally activatable, DNAzyme-based sensing technology that enables compartment-specific of ions through ribosomal RNA (rRNA) regulated signal amplification. The system leverages subcellularly encoded rRNA activate sensors, and further drives amplification via multiple turnover cleavage molecular beacons, significantly enhance sensitivity precision metal-ion organelles (e.g. mitochondria) or membraneless cytosol). Furthermore, demonstrate the allows situ monitoring dynamics mitochondrial Zn

Language: Английский