Closed-loop cascade nanozyme strategy for mutually reinforced catalytic and mild-temperature photothermal therapeutic effects

Abstract Nanocatalysis coupled with photothermal therapy is a potent anti-cancer approach, yet its clinical utility is limited by low concentration of tumor substrate, redox interference, and risks of overheating normal tissues. Herein, we propose an innovative closed-loop nanozyme approach that lev...

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Main Authors: Fan Yang, Chunyu Yan, Nannan Li, Xinxiu Jiang, Baojie Du, Peirong Bai, Liping Li, Ruiping Zhang
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03320-2
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author Fan Yang
Chunyu Yan
Nannan Li
Xinxiu Jiang
Baojie Du
Peirong Bai
Liping Li
Ruiping Zhang
author_facet Fan Yang
Chunyu Yan
Nannan Li
Xinxiu Jiang
Baojie Du
Peirong Bai
Liping Li
Ruiping Zhang
author_sort Fan Yang
collection DOAJ
description Abstract Nanocatalysis coupled with photothermal therapy is a potent anti-cancer approach, yet its clinical utility is limited by low concentration of tumor substrate, redox interference, and risks of overheating normal tissues. Herein, we propose an innovative closed-loop nanozyme approach that leverages the synergistic effects of catalytic and mild photothermal therapy (mPTT) to address aforementioned challenges. The strategy features a folic acid-functionalized iron single-atom catalyst (FeNC-FA), designed to exhibit exceptional multienzymatic capabilities and an optimal photothermal response. In the system, the engineered FeNC-FA is capable of inducing reactive oxygen species (ROS) storm and depleting glutathione (GSH) in the specific tumor microenvironment (TME) to initiate ferroptosis. Concurrently, the accumulation of ROS effectively cleaves heat shock proteins (HSPs), thereby enhancing mPTT. An intriguing aspect is that the increased temperature within the TME further facilitates the conversion of H2O2 to O2, alleviating hypoxia and providing a positive feedback circuit to boost catalytic therapy. Additionally, the advanced photoacoustic (PA) imaging capabilities of FeNC-FA allow for self-monitoring of their accumulation at tumor sites, thereby guiding the mPTT process. Taken together, it provides a PA image-guided, mutually reinforced catalytic and mild photothermal synergistic tumor therapy both in vitro and in vivo. This targeted and synergistic strategy holds great promise for personalized medicine applications.
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spelling doaj-art-a040aa0ceff142618bc94e1b06427a962025-08-20T02:25:41ZengBMCJournal of Nanobiotechnology1477-31552025-04-0123111110.1186/s12951-025-03320-2Closed-loop cascade nanozyme strategy for mutually reinforced catalytic and mild-temperature photothermal therapeutic effectsFan Yang0Chunyu Yan1Nannan Li2Xinxiu Jiang3Baojie Du4Peirong Bai5Liping Li6Ruiping Zhang7Basic Medical College, Research Institute of Circadian Rhythm and Disease, Academy of Medical Sciences, Shanxi Medical UniversityBasic Medical College, Research Institute of Circadian Rhythm and Disease, Academy of Medical Sciences, Shanxi Medical UniversityBasic Medical College, Research Institute of Circadian Rhythm and Disease, Academy of Medical Sciences, Shanxi Medical UniversityBasic Medical College, Research Institute of Circadian Rhythm and Disease, Academy of Medical Sciences, Shanxi Medical UniversityShanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Shanxi HospitalShanxi Bethune Hospital, Third Hospital of Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Shanxi HospitalBasic Medical College, Research Institute of Circadian Rhythm and Disease, Academy of Medical Sciences, Shanxi Medical UniversityThe Radiology Department of Shanxi Provincial People’s Hospital, Five Hospital of Shanxi Medical UniversityAbstract Nanocatalysis coupled with photothermal therapy is a potent anti-cancer approach, yet its clinical utility is limited by low concentration of tumor substrate, redox interference, and risks of overheating normal tissues. Herein, we propose an innovative closed-loop nanozyme approach that leverages the synergistic effects of catalytic and mild photothermal therapy (mPTT) to address aforementioned challenges. The strategy features a folic acid-functionalized iron single-atom catalyst (FeNC-FA), designed to exhibit exceptional multienzymatic capabilities and an optimal photothermal response. In the system, the engineered FeNC-FA is capable of inducing reactive oxygen species (ROS) storm and depleting glutathione (GSH) in the specific tumor microenvironment (TME) to initiate ferroptosis. Concurrently, the accumulation of ROS effectively cleaves heat shock proteins (HSPs), thereby enhancing mPTT. An intriguing aspect is that the increased temperature within the TME further facilitates the conversion of H2O2 to O2, alleviating hypoxia and providing a positive feedback circuit to boost catalytic therapy. Additionally, the advanced photoacoustic (PA) imaging capabilities of FeNC-FA allow for self-monitoring of their accumulation at tumor sites, thereby guiding the mPTT process. Taken together, it provides a PA image-guided, mutually reinforced catalytic and mild photothermal synergistic tumor therapy both in vitro and in vivo. This targeted and synergistic strategy holds great promise for personalized medicine applications.https://doi.org/10.1186/s12951-025-03320-2Single-atom nanozymeNanocatalytic therapyPA imaging guided-synergistic therapyMild-temperature photothermal therapyClosed-loop strategy
spellingShingle Fan Yang
Chunyu Yan
Nannan Li
Xinxiu Jiang
Baojie Du
Peirong Bai
Liping Li
Ruiping Zhang
Closed-loop cascade nanozyme strategy for mutually reinforced catalytic and mild-temperature photothermal therapeutic effects
Journal of Nanobiotechnology
Single-atom nanozyme
Nanocatalytic therapy
PA imaging guided-synergistic therapy
Mild-temperature photothermal therapy
Closed-loop strategy
title Closed-loop cascade nanozyme strategy for mutually reinforced catalytic and mild-temperature photothermal therapeutic effects
title_full Closed-loop cascade nanozyme strategy for mutually reinforced catalytic and mild-temperature photothermal therapeutic effects
title_fullStr Closed-loop cascade nanozyme strategy for mutually reinforced catalytic and mild-temperature photothermal therapeutic effects
title_full_unstemmed Closed-loop cascade nanozyme strategy for mutually reinforced catalytic and mild-temperature photothermal therapeutic effects
title_short Closed-loop cascade nanozyme strategy for mutually reinforced catalytic and mild-temperature photothermal therapeutic effects
title_sort closed loop cascade nanozyme strategy for mutually reinforced catalytic and mild temperature photothermal therapeutic effects
topic Single-atom nanozyme
Nanocatalytic therapy
PA imaging guided-synergistic therapy
Mild-temperature photothermal therapy
Closed-loop strategy
url https://doi.org/10.1186/s12951-025-03320-2
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