Nano Self-Assembly for Apoptosis Induction and Early Therapeutic Efficacy Monitoring

Real-time monitoring of early antitumor efficacy is one of the key issues in realizing high-efficiency and more precise tumor treatment. As a highly specific event in the early stage of apoptosis, the release of cytochrome c may act as a key biomarker for monitoring cell apoptosis. However, achievin...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2023-09, Vol.95 (38), p.14421-14429
Main Authors: Meng, Xiaoyi, Cheng, Yue, Wang, Fang, Sun, Zhaogang, Chu, Hongqian, Wang, Yong
Format: Article
Language:English
Subjects:
Analytical chemistry
Anticancer properties
Antitumor activity
Apoptosis
Biomarkers
Chemistry
Cytochrome
Cytochrome c
Cytochromes
Damage
Deoxyribonucleic acid
DNA
Effectiveness
Ferrous ions
Fluorescence
Ions
Mitochondria
Monitoring
Nanoparticles
Reactive oxygen species
Real time
Self-assembly
Tumors
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Summary:Real-time monitoring of early antitumor efficacy is one of the key issues in realizing high-efficiency and more precise tumor treatment. As a highly specific event in the early stage of apoptosis, the release of cytochrome c may act as a key biomarker for monitoring cell apoptosis. However, achieving real-time monitoring of the cytochrome c release in vivo remains a challenge. Herein, we report a novel integrated nanosystem named DFeK nanoparticle (DFeK NP) to achieve a favorable collaboration of inducing tumor cell apoptosis and monitoring early therapeutic efficacy, which combined the cytochrome c-activated DNA nanoprobe cApt-App with pro-apoptotic peptide [KLAKLAK]2 and ferrous ions. [KLAKLAK]2 can target the mitochondria to disrupt the mitochondrial membrane together with reactive oxygen species produced by ferrous ions via the Fenton reaction to promote mitochondrial damage. Then, cytochrome c is released from damaged mitochondria to trigger apoptosis, further activating the cApt-App probe from the fluorescence “off” state to the “on” state. The cytochrome c-specific “off-to-on” transition was successfully applied in fluorescence imaging of cytochrome c in vivo and thus achieved real-time early therapeutic efficacy monitoring. Collectively, this work presents a valuable integrated tool for tumor inhibition and therapeutic efficacy evaluation to realize more precise and more effective tumor treatment.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.3c02860