Switching Reactive Oxygen Species into Reactive Nitrogen Species by Photocleaved O 2 -Released Nanoplatforms Favors Hypoxic Tumor Repression

In various reactive oxygen species (ROS)-based antitumor approaches (e.g., photodynamic therapy), increasing attentions are made to improve ROS level, but the short lifetime that is another decisive hurdle of ROS-based antitumor outcomes is not even explored yet. To address it, a photocleaved O -rel...

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Bibliographic Details
Published in:Advanced science 2021-10, Vol.8 (19), p.e2101065
Main Authors: Luo, Tao, Wang, Duo, Liu, Lidong, Zhang, Yan, Han, Chuangye, Xie, Ying, Liu, Yan, Liang, Jingchen, Qiu, Guanhua, Li, Hongxue, Su, Danke, Liu, Junjie, Zhang, Kun
Format: Article
Language:English
Subjects:
Animals
Breast Neoplasms - complications
Breast Neoplasms - metabolism
Breast Neoplasms - therapy
Disease Models, Animal
Female
Humans
Hypoxia - complications
Hypoxia - metabolism
Hypoxia - therapy
Mice
Mice, Nude
Nanoparticles
Oxygen - metabolism
Photochemotherapy - methods
Reactive Nitrogen Species - metabolism
Reactive Oxygen Species - metabolism
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Summary:In various reactive oxygen species (ROS)-based antitumor approaches (e.g., photodynamic therapy), increasing attentions are made to improve ROS level, but the short lifetime that is another decisive hurdle of ROS-based antitumor outcomes is not even explored yet. To address it, a photocleaved O -released nanoplatform is constructed to release and switch ROS into reactive nitrogen species (RNS) for repressing hypoxic breast tumor. Systematic explorations validate that the nanoplatforms can attain continuous photocontrolled O release, alleviate hypoxia, and elevate ROS level. More significantly, the entrapped PDE5 inhibitor (PDE5-i) in this nanoplatform can be enzymatically decomposed into nitric oxide that further combines with ROS to generate RNS, enabling the persistent antitumor effect since RNS features longer lifetime than ROS. Intriguingly, ROS conversion into RNS can help ROS to evade the hypoxia-induced resistance to ROS-based antitumor. Eventually, RNS production unlocks robust antitumor performances along with ROS elevation and hypoxia mitigation. Moreover, this extraordinary conversion from ROS into RNS also can act as a general method to solve the short lifetime of ROS.
ISSN:2198-3844
2198-3844
DOI:10.1002/advs.202101065