O2-self-supplying and glutathione-depleting scaffold for synergistic cancer therapy

Photodynamic therapy (PDT) has great potential for tumor therapy because of its non-invasive and high selectivity. However, the therapeutic effect of PDT is critically restricted by hypoxia and glutathione (GSH) overexpression in the tumor microenvironment (TME). In this work, CeO2 with catalase and...

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Main Authors: Jiajia Zeng, Chongxian He, Xinna Bai, Cijun Shuai, Hao Pan
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Polymer Testing
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Online Access:http://www.sciencedirect.com/science/article/pii/S0142941824003337
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author Jiajia Zeng
Chongxian He
Xinna Bai
Cijun Shuai
Hao Pan
author_facet Jiajia Zeng
Chongxian He
Xinna Bai
Cijun Shuai
Hao Pan
author_sort Jiajia Zeng
collection DOAJ
description Photodynamic therapy (PDT) has great potential for tumor therapy because of its non-invasive and high selectivity. However, the therapeutic effect of PDT is critically restricted by hypoxia and glutathione (GSH) overexpression in the tumor microenvironment (TME). In this work, CeO2 with catalase and peroxidase dual enzyme activities was loaded on Ti3C2 nano-sheet, and the nanosystem was then introduced in poly-L-lactic acid (PLLA) and prepared into bone scaffold using selective laser sintering technology. Specifically, CeO2 alleviates hypoxia through its catalase enzyme activity, which promotes the continuous photodynamic process. CeO2 also consumes over-expressed GSH through its redox reaction and amplifies the oxidative stress in TME, thus improving the curative effect of PDT. On the other hand, the photothermal effect of scaffold can not only generate heat to kill tumor cells, but also enhance the activity of nanoenzyme, and the catalase activity enhanced by photothermal effect is fed back to PDT, forming a two-way promotion. The results indicated that the concentration of oxygen in PLLA/Ti3C2-CeO2 scaffold group was 9.76 mg/L higher, and the concentration of singlet oxygen (1O2) and hydroxyl radical (·OH) was respectively increased by 60 % and 170 %, compared with the PLLA/Ti3C2 scaffold. Moreover, the PLLA/Ti3C2-CeO2 scaffold showed a higher GSH consumption rate, indicating that it could consume the overexpressed GSH. Therefore, the Ti3C2 nano-sheet loaded with CeO2 could combine the dual enzyme activities, photodynamic and photothermal effect to enhance the tumor therapy with a tumor growth inhibitory effect of approximately 88.8 %. In summary, introducing the Ti3C2 nanosystem loaded with nanozyme into PLLA scaffold is a promising strategy to develop bone scaffold with multimodal anti-tumor function.
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spelling doaj-art-cccd6b9b2eb748f0876ab8ff52f6bfb62025-01-12T05:24:05ZengElsevierPolymer Testing1873-23482025-01-01142108656O2-self-supplying and glutathione-depleting scaffold for synergistic cancer therapyJiajia Zeng0Chongxian He1Xinna Bai2Cijun Shuai3Hao Pan4Hunan 3D Printing Engineering Research Center of Oral Care, Department of Periodontics, Xiangya Stomatological Hospital and Xiangya School of Stomatology, Central South University, 72 Xiangya Road, 410008, Changsha, Hunan, ChinaInstitute of Additive Manufacturing, Jiangxi University of Science and Technology, Nanchang, 330013, ChinaHunan 3D Printing Engineering Research Center of Oral Care, Department of Conservative Dentistry and Endodontics, Xiangya Stomatological Hospital and Xiangya School of Stomatology, Central South University, 72 Xiangya Road, 410008, Changsha, Hunan, ChinaJiangxi Province Key Laboratory of Additive Manufacturing of Implantable Medical Device, Jiangxi University of Science and Technology, Nanchang, 330013, China; State Key Laboratory of Precision Manufacturing for Extreme Service Performance, College of Mechanical and Electrical Engineering, Central South University, Changsha, 410083, China; Corresponding author. Jiangxi Province Key Laboratory of Additive Manufacturing of Implantable Medical Device, Jiangxi University of Science and Technology, Nanchang, 330013, China.Hunan 3D Printing Engineering Research Center of Oral Care, Department of Periodontics, Xiangya Stomatological Hospital and Xiangya School of Stomatology, Central South University, 72 Xiangya Road, 410008, Changsha, Hunan, China; Corresponding author.Photodynamic therapy (PDT) has great potential for tumor therapy because of its non-invasive and high selectivity. However, the therapeutic effect of PDT is critically restricted by hypoxia and glutathione (GSH) overexpression in the tumor microenvironment (TME). In this work, CeO2 with catalase and peroxidase dual enzyme activities was loaded on Ti3C2 nano-sheet, and the nanosystem was then introduced in poly-L-lactic acid (PLLA) and prepared into bone scaffold using selective laser sintering technology. Specifically, CeO2 alleviates hypoxia through its catalase enzyme activity, which promotes the continuous photodynamic process. CeO2 also consumes over-expressed GSH through its redox reaction and amplifies the oxidative stress in TME, thus improving the curative effect of PDT. On the other hand, the photothermal effect of scaffold can not only generate heat to kill tumor cells, but also enhance the activity of nanoenzyme, and the catalase activity enhanced by photothermal effect is fed back to PDT, forming a two-way promotion. The results indicated that the concentration of oxygen in PLLA/Ti3C2-CeO2 scaffold group was 9.76 mg/L higher, and the concentration of singlet oxygen (1O2) and hydroxyl radical (·OH) was respectively increased by 60 % and 170 %, compared with the PLLA/Ti3C2 scaffold. Moreover, the PLLA/Ti3C2-CeO2 scaffold showed a higher GSH consumption rate, indicating that it could consume the overexpressed GSH. Therefore, the Ti3C2 nano-sheet loaded with CeO2 could combine the dual enzyme activities, photodynamic and photothermal effect to enhance the tumor therapy with a tumor growth inhibitory effect of approximately 88.8 %. In summary, introducing the Ti3C2 nanosystem loaded with nanozyme into PLLA scaffold is a promising strategy to develop bone scaffold with multimodal anti-tumor function.http://www.sciencedirect.com/science/article/pii/S0142941824003337NanozymesScaffoldImprove hypoxiaGlutathione depletionHyperthermia-enhancedSynergetic therapy
spellingShingle Jiajia Zeng
Chongxian He
Xinna Bai
Cijun Shuai
Hao Pan
O2-self-supplying and glutathione-depleting scaffold for synergistic cancer therapy
Polymer Testing
Nanozymes
Scaffold
Improve hypoxia
Glutathione depletion
Hyperthermia-enhanced
Synergetic therapy
title O2-self-supplying and glutathione-depleting scaffold for synergistic cancer therapy
title_full O2-self-supplying and glutathione-depleting scaffold for synergistic cancer therapy
title_fullStr O2-self-supplying and glutathione-depleting scaffold for synergistic cancer therapy
title_full_unstemmed O2-self-supplying and glutathione-depleting scaffold for synergistic cancer therapy
title_short O2-self-supplying and glutathione-depleting scaffold for synergistic cancer therapy
title_sort o2 self supplying and glutathione depleting scaffold for synergistic cancer therapy
topic Nanozymes
Scaffold
Improve hypoxia
Glutathione depletion
Hyperthermia-enhanced
Synergetic therapy
url http://www.sciencedirect.com/science/article/pii/S0142941824003337
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AT chongxianhe o2selfsupplyingandglutathionedepletingscaffoldforsynergisticcancertherapy
AT xinnabai o2selfsupplyingandglutathionedepletingscaffoldforsynergisticcancertherapy
AT cijunshuai o2selfsupplyingandglutathionedepletingscaffoldforsynergisticcancertherapy
AT haopan o2selfsupplyingandglutathionedepletingscaffoldforsynergisticcancertherapy