Mitochondria-targeted delivery and light controlled release of iron prodrug and CO to enhance cancer therapy by ferroptosis

Mitochondrial malfunction is considered to be a decisive signal of apoptosis. It would be a promising strategy to target mitochondria in cancer cells to generate reactive oxygen species (ROS), thus directly inducing mitochondrial damage. We herein reported a mitochondria-targeted, photo-responsive p...

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Published inNew journal of chemistry Vol. 44; no. 8; pp. 3478 - 3486
Main Authors Gao, Fan, Wang, Fei, Nie, Xuan, Zhang, Ze, Chen, Guang, Xia, Lei, Wang, Long-Hai, Wang, Chang-Hui, Hao, Zong-Yao, Zhang, Wen-Jian, Hong, Chun-Yan, You, Ye-Zi
Format Journal Article
LanguageEnglish
Published Cambridge Royal Society of Chemistry 28.02.2020
Subjects
Apoptosis
Cancer
Cancer therapies
Carbon monoxide
Chemical compounds
Controlled release
Damage
Drugs
Hydrophobicity
Iron
Mitochondria
Nanoparticles
Synergistic effect
Therapy
Ultraviolet radiation
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Summary:Mitochondrial malfunction is considered to be a decisive signal of apoptosis. It would be a promising strategy to target mitochondria in cancer cells to generate reactive oxygen species (ROS), thus directly inducing mitochondrial damage. We herein reported a mitochondria-targeted, photo-responsive polymer (Mito-PNBE), which can self-assemble into nanoparticles (Fe-CO@Mito-PNBE) encapsulated with diphenylcyclopropenone (light-responsive CO prodrugs) and aminoferrocene-based prodrugs via hydrophobic interactions. Upon UV-irradiation, the rapid release of CO and aminoferrocene-based prodrugs caused by disassembly was observed. On one hand, the released carbon monoxide in mitochondria could enhance ROS generation and accelerate oxidative metabolism. On the other hand, the aminoferrocene-based prodrugs will release Fe 3+ /Fe 2+ ions in the tumor microenvironment, thus triggering the Fenton reaction, which generates more ROS and damages the mitochondria. Thus, the synergistic effect of the two drugs produces enough amounts of ROS in the mitochondria, leading to mitochondrial collapse with an enhanced cancer therapeutic effect. This multifunctional platform has potential in precision cancer therapy. Mitochondrial malfunction is considered to be a decisive signal of apoptosis.
Bibliography:10.1039/c9nj05860e
Electronic supplementary information (ESI) available. See DOI
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
ISSN:1144-0546
1369-9261
DOI:10.1039/c9nj05860e