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

• Published in: Angewandte Chemie International Edition Vol. 61; no. 28; pp. e202203238 - n/a
• Main Authors: Yu, Fangzhi, Shao, Yulei, Chai, Xin, Zhao, Yuliang, Li, Lele
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 11.07.2022
• Edition: International ed. in English
• Subjects: Deoxyribonucleic acid; DNA; DNA Sensor Probes; Endonuclease; Enzyme Activity Imaging; Enzyme inhibitors; Mitochondria; Nanoparticles; Near infrared radiation; Oxidative stress; Photodynamic Therapy; Subcellular Dynamics; Mitochondria; DNA Sensor Probes; Photodynamic Therapy; Enzyme Activity Imaging; Subcellular Dynamics
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202203238

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. A multifunctional nanoplatform was constructed for in situ imaging of the subcellular enzyme dynamics in response to near‐infrared light‐triggered, mitochondria‐targeted photodynamic therapy (PDT). With this versatile nanodevice, mitochondrial accumulation of specific enzymes was visualized in response to the increased concentration of reactive oxygen species during PDT.