Tumor Microenvironment-Modulated Nanozymes for NIR-II-Triggered Hyperthermia-Enhanced Photo-Nanocatalytic Therapy via Disrupting ROS Homeostasis.

Content Provider	Europe PMC
Author	Zhu, Lipeng Dai, Yunlu Gao, Lizeng Zhao, Qi
Copyright Year	2021
Abstract	PurposeReactive oxygen species (ROS) are a group of signaling biomolecules that play important roles in the cell cycle. When intracellular ROS homeostasis is disrupted, it can induce cellular necrosis and apoptosis. It is desirable to effectively cascade-amplifying ROS generation and weaken antioxidant defense for disrupting ROS homeostasis in tumor microenvironment (TME), which has been recognized as a novel and ideal antitumor strategy. Multifunctional nanozymes are highly promising agents for ROS-mediated therapy.MethodsThis study constructed a novel theranostic nanoagent based on PEG@Cu2-xS@Ce6 nanozymes (PCCNs) through a facile one-step hydrothermal method. We systematically investigated the photodynamic therapy (PDT)/photothermal therapy (PTT) properties, catalytic therapy (CTT) and glutathione (GSH) depletion activities of PCCNs, antitumor efficacy induced by PCCNs in vitro and in vivo.ResultsPCCNs generate singlet oxygen (1O2) with laser (660 nm) irradiation and use catalytic reactions to produce hydroxyl radical (•OH). Moreover, PCCNs show the high photothermal performance under NIR II 1064-nm laser irradiation, which can enhance CTT/PDT efficiencies to increase ROS generation. The properties of O2 evolution and GSH consumption of PCCNs achieve hypoxia-relieved PDT and destroy cellular antioxidant defense system respectively. The excellent antitumor efficacy in 4T1 tumor-bearing mice of PCCNs is achieved through disrupting ROS homeostasis-involved therapy under the guidance of photothermal/photoacoustic imaging.ConclusionOur study provides a proof of concept of “all-in-one” nanozymes to eliminate tumors via disrupting ROS homeostasis.
Page Count	19
ISSN	11769114
Journal	International Journal of Nanomedicine
Volume Number	16
PubMed Central reference number	PMC8275154
PubMed reference number	34267513
e-ISSN	11782013
DOI	10.2147/ijn.s309062
Language	English
Publisher	Dove Medical Press
Publisher Date	2021-07-05
Access Restriction	Open
Rights License	This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). © 2021 Zhu et al.
Subject Keyword	ROS homeostasis nanozyme tumor microenvironment catalytic therapy photodynamic/photothermal therapy photothermal/photoacoustic imaging
Content Type	Text
Resource Type	Article
Subject	Nanoscience and Nanotechnology Organic Chemistry Drug Discovery Medicine Biomaterials Biophysics Bioengineering Pharmaceutical Science