TY - JOUR
T1 - Spatially Selective Monitoring of Subcellular Enzyme Dynamics in Response to Mitochondria-Targeted Photodynamic Therapy
AU - Yu, Fangzhi
AU - Shao, Yulei
AU - Chai, Xin
AU - Zhao, Yuliang
AU - Li, Lele
N1 - Funding Information:
This work was supported financially by the NSFC (22125402), the Beijing Natural Science Foundation (JQ20005), and the National Key R&D Program of China (2021YFA1200104).
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022/7/11
Y1 - 2022/7/11
N2 - 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.
AB - 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.
KW - DNA Sensor Probes
KW - Enzyme Activity Imaging
KW - Mitochondria
KW - Photodynamic Therapy
KW - Subcellular Dynamics
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U2 - 10.1002/anie.202203238
DO - 10.1002/anie.202203238
M3 - Article
C2 - 35412703
AN - SCOPUS:85128868808
SN - 1433-7851
VL - 61
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 28
M1 - e202203238
ER -