Cooperation of endogenous and exogenous reactive oxygen species induced by zinc peroxide nanoparticles to enhance oxidative stress-based cancer therapy
Reactive oxygen species (ROS)-generating anticancer agents can act through two different mechanisms: (i) elevation of endogenous ROS production in mitochondria, or (ii) formation/delivery of exogenous ROS within cells. However, there is a lack of research on the development of ROS-generating nanosys...
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Published in | Theranostics Vol. 9; no. 24; pp. 7200 - 7209 |
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Main Authors | , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Australia
Ivyspring International Publisher Pty Ltd
01.01.2019
Ivyspring International Publisher |
Subjects | |
Online Access | Get full text |
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Summary: | Reactive oxygen species (ROS)-generating anticancer agents can act through two different mechanisms: (i) elevation of endogenous ROS production in mitochondria, or (ii) formation/delivery of exogenous ROS within cells. However, there is a lack of research on the development of ROS-generating nanosystems that combine endogenous and exogenous ROS to enhance oxidative stress-mediated cancer cell death.
A ROS-generating agent based on polymer-modified zinc peroxide nanoparticles (ZnO
NPs) was presented, which simultaneously delivered exogenous H
O
and Zn
capable of amplifying endogenous ROS production for synergistic cancer therapy.
After internalization into tumor cells, ZnO
NPs underwent decomposition in response to mild acidic pH, resulting in controlled release of H
O
and Zn
. Intriguingly, Zn
could increase the production of mitochondrial O
·
and H
O
by inhibiting the electron transport chain, and thus exerted anticancer effect in a synergistic manner with the exogenously released H
O
to promote cancer cell killing. Furthermore, ZnO
NPs were doped with manganese
cation exchange, making them an activatable magnetic resonance imaging contrast agent.
This study establishes a ZnO
-based theranostic nanoplatform which achieves enhanced oxidative damage to cancer cells by a two-pronged approach of combining endogenous and exogenous ROS. |
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Bibliography: | These authors contributed equally to this work. Competing Interests: The authors have declared that no competing interest exists. |
ISSN: | 1838-7640 1838-7640 |
DOI: | 10.7150/thno.39831 |