NIR-triggering cobalt single-atom enzyme switches off-to-on for boosting the interactive dynamic effects of multimodal phototherapy

Abstract Noninvasive phototherapy with functional preservation is considered to be a promising cancer therapeutic method. However, the clinical application of tumor phototherapy is severely restrained by the lack of appropriate multimodal phototherapy agents exhibiting an ideal tissue penetration de...

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Main Authors: Hao Dai, Ali Han, Xijun Wang, Peng Zhu, Dingsheng Wang, Yuguang Wang
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-57188-9
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author Hao Dai
Ali Han
Xijun Wang
Peng Zhu
Dingsheng Wang
Yuguang Wang
author_facet Hao Dai
Ali Han
Xijun Wang
Peng Zhu
Dingsheng Wang
Yuguang Wang
author_sort Hao Dai
collection DOAJ
description Abstract Noninvasive phototherapy with functional preservation is considered to be a promising cancer therapeutic method. However, the clinical application of tumor phototherapy is severely restrained by the lack of appropriate multimodal phototherapy agents exhibiting an ideal tissue penetration depth to maximize the antitumor efficiency as well as to maintain important tissue functions. Herein, an innovative near-infrared ray (NIR)-triggered photodynamic-photocatalytic-photothermal therapy (PDT-PCT-PTT) agent based on an atomically dispersed cobalt single-atom enzyme (Co-SAE) anchored on hollow N-doped carbon sphere (HNCS) has been strategically developed. Reactive oxygen species (ROS) are highly activated and amplified through both the photogenerated electrons and the photothermal conversion induced by NIR irradiation, as systematically demonstrated by the experimental and density functional theory (DFT) calculation results. Mild hyperthermia is eventually achieved through apoptosis and ferroptosis caused by ROS, significantly boosting the interaction of ROS dynamic effects and thermodynamic effects in the tumor microenvironment (TME). More importantly, Co-SAEs/HNCS not only causes multimodal damage through limited TME products but also preserves important organ functions by the induction of mild local hyperthermia. This work expands the biomedical application field of SAEs and presents an innovative all-in-one, multimodal concept for the noninvasive treatment of head and neck cancer.
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spelling doaj-art-0133fd507c4a4271aee08bff413ec3532025-08-20T03:04:20ZengNature PortfolioNature Communications2041-17232025-02-0116111710.1038/s41467-025-57188-9NIR-triggering cobalt single-atom enzyme switches off-to-on for boosting the interactive dynamic effects of multimodal phototherapyHao Dai0Ali Han1Xijun Wang2Peng Zhu3Dingsheng Wang4Yuguang Wang5Department of General Dentistry II/Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials & Central Laboratory Peking University School and HospitalDepartment of Chemistry, Tsinghua UniversityDepartment of Chemical and Biological Engineering, Northwestern UniversityDepartment of Chemistry, Tsinghua UniversityDepartment of Chemistry, Tsinghua UniversityDepartment of General Dentistry II/Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices Beijing Key Laboratory of Digital Stomatology & NHC Key Laboratory of Digital Stomatology & NMPA Key Laboratory for Dental Materials & Central Laboratory Peking University School and HospitalAbstract Noninvasive phototherapy with functional preservation is considered to be a promising cancer therapeutic method. However, the clinical application of tumor phototherapy is severely restrained by the lack of appropriate multimodal phototherapy agents exhibiting an ideal tissue penetration depth to maximize the antitumor efficiency as well as to maintain important tissue functions. Herein, an innovative near-infrared ray (NIR)-triggered photodynamic-photocatalytic-photothermal therapy (PDT-PCT-PTT) agent based on an atomically dispersed cobalt single-atom enzyme (Co-SAE) anchored on hollow N-doped carbon sphere (HNCS) has been strategically developed. Reactive oxygen species (ROS) are highly activated and amplified through both the photogenerated electrons and the photothermal conversion induced by NIR irradiation, as systematically demonstrated by the experimental and density functional theory (DFT) calculation results. Mild hyperthermia is eventually achieved through apoptosis and ferroptosis caused by ROS, significantly boosting the interaction of ROS dynamic effects and thermodynamic effects in the tumor microenvironment (TME). More importantly, Co-SAEs/HNCS not only causes multimodal damage through limited TME products but also preserves important organ functions by the induction of mild local hyperthermia. This work expands the biomedical application field of SAEs and presents an innovative all-in-one, multimodal concept for the noninvasive treatment of head and neck cancer.https://doi.org/10.1038/s41467-025-57188-9
spellingShingle Hao Dai
Ali Han
Xijun Wang
Peng Zhu
Dingsheng Wang
Yuguang Wang
NIR-triggering cobalt single-atom enzyme switches off-to-on for boosting the interactive dynamic effects of multimodal phototherapy
Nature Communications
title NIR-triggering cobalt single-atom enzyme switches off-to-on for boosting the interactive dynamic effects of multimodal phototherapy
title_full NIR-triggering cobalt single-atom enzyme switches off-to-on for boosting the interactive dynamic effects of multimodal phototherapy
title_fullStr NIR-triggering cobalt single-atom enzyme switches off-to-on for boosting the interactive dynamic effects of multimodal phototherapy
title_full_unstemmed NIR-triggering cobalt single-atom enzyme switches off-to-on for boosting the interactive dynamic effects of multimodal phototherapy
title_short NIR-triggering cobalt single-atom enzyme switches off-to-on for boosting the interactive dynamic effects of multimodal phototherapy
title_sort nir triggering cobalt single atom enzyme switches off to on for boosting the interactive dynamic effects of multimodal phototherapy
url https://doi.org/10.1038/s41467-025-57188-9
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