Tailored biomimetic nanoreactor improves glioma chemodynamic treatment via triple glutathione depletion and prompt acidity elevation
Chemodynamic therapy (CDT) is an emerging antitumor strategy utilizing iron-initiated Fenton reaction to destroy tumor cells by converting endogenous H2O2 into highly toxic hydroxyl radical (OH). However, the intratumoral overexpressed glutathione (GSH) and deficient acid greatly reduce CDT efficacy...
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Elsevier
2025-02-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425000055 |
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| author | Ya Wen Qiansai Qiu Feng Feng Yujuan Zhu Jianquan Zhang Zesheng Sun Tuodi Zhang Wei Shi Jinlong Shi |
| author_facet | Ya Wen Qiansai Qiu Feng Feng Yujuan Zhu Jianquan Zhang Zesheng Sun Tuodi Zhang Wei Shi Jinlong Shi |
| author_sort | Ya Wen |
| collection | DOAJ |
| description | Chemodynamic therapy (CDT) is an emerging antitumor strategy utilizing iron-initiated Fenton reaction to destroy tumor cells by converting endogenous H2O2 into highly toxic hydroxyl radical (OH). However, the intratumoral overexpressed glutathione (GSH) and deficient acid greatly reduce CDT efficacy because of OH scavenging and decreased OH production efficiency. Even worse, the various physiological barriers, especially in glioma, further put the brakes on the targeted delivery of Fenton agents. Herein, by exploring the thiol reaction potential of 5,5′-dithiobis-2-nitrobenzoic acid (DTNB), we have constructed a tailored biomimetic nanoreactor to improve glioma CDT efficacy through synchronous GSH exhaustion and acidity elevation. The biomimetic nanoreactor was fabricated by employing DTNB to drive the nano-assembly of BSA molecules, followed by loading the carrier onto the cell surface of neutrophils via disulfide-thiol exchange. Upon sensing the inflammatory signal, the nanoreactor hijacked by neutrophils efficiently targets to the tumor site, which then dually depletes GSH by disulfide bond stabilizing the nanostructure and the following liberated Fe (III). In particular, the simultaneously released DTNB can not only consume the residual GSH, but also produce 5-thio-2-nitrobenzoic acid (TNB) promptly, resulting in accelerated Fenton reaction. Through in vitro and in vivo experiments, we demonstrate the exhaustive and synchronous regulation of Fenton chemistry could potentially serve as a novel CDT strategy for glioma. |
| format | Article |
| id | doaj-art-932137d9f3064eaebd7d2bdbdff6c88b |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-932137d9f3064eaebd7d2bdbdff6c88b2025-01-17T04:52:16ZengElsevierMaterials Today Bio2590-00642025-02-0130101447Tailored biomimetic nanoreactor improves glioma chemodynamic treatment via triple glutathione depletion and prompt acidity elevationYa Wen0Qiansai Qiu1Feng Feng2Yujuan Zhu3Jianquan Zhang4Zesheng Sun5Tuodi Zhang6Wei Shi7Jinlong Shi8Department of Neurosurgery, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, ChinaDepartment of Radiology, Tumor Hospital Affiliated to Nantong University, Nantong, 226001, ChinaDepartment of Radiology, Tumor Hospital Affiliated to Nantong University, Nantong, 226001, ChinaDepartment of Neurosurgery, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, ChinaDepartment of Radiology, Tumor Hospital Affiliated to Nantong University, Nantong, 226001, ChinaDepartment of Neurosurgery, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, ChinaDepartment of Neurosurgery, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, ChinaDepartment of Neurosurgery, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, ChinaDepartment of Neurosurgery, Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong University, Nantong, 226001, China; Corresponding author.Chemodynamic therapy (CDT) is an emerging antitumor strategy utilizing iron-initiated Fenton reaction to destroy tumor cells by converting endogenous H2O2 into highly toxic hydroxyl radical (OH). However, the intratumoral overexpressed glutathione (GSH) and deficient acid greatly reduce CDT efficacy because of OH scavenging and decreased OH production efficiency. Even worse, the various physiological barriers, especially in glioma, further put the brakes on the targeted delivery of Fenton agents. Herein, by exploring the thiol reaction potential of 5,5′-dithiobis-2-nitrobenzoic acid (DTNB), we have constructed a tailored biomimetic nanoreactor to improve glioma CDT efficacy through synchronous GSH exhaustion and acidity elevation. The biomimetic nanoreactor was fabricated by employing DTNB to drive the nano-assembly of BSA molecules, followed by loading the carrier onto the cell surface of neutrophils via disulfide-thiol exchange. Upon sensing the inflammatory signal, the nanoreactor hijacked by neutrophils efficiently targets to the tumor site, which then dually depletes GSH by disulfide bond stabilizing the nanostructure and the following liberated Fe (III). In particular, the simultaneously released DTNB can not only consume the residual GSH, but also produce 5-thio-2-nitrobenzoic acid (TNB) promptly, resulting in accelerated Fenton reaction. Through in vitro and in vivo experiments, we demonstrate the exhaustive and synchronous regulation of Fenton chemistry could potentially serve as a novel CDT strategy for glioma.http://www.sciencedirect.com/science/article/pii/S2590006425000055Biomimetic nanoreactorGSH exhaustionAcidity elevationChemodynamic therapyGlioma |
| spellingShingle | Ya Wen Qiansai Qiu Feng Feng Yujuan Zhu Jianquan Zhang Zesheng Sun Tuodi Zhang Wei Shi Jinlong Shi Tailored biomimetic nanoreactor improves glioma chemodynamic treatment via triple glutathione depletion and prompt acidity elevation Materials Today Bio Biomimetic nanoreactor GSH exhaustion Acidity elevation Chemodynamic therapy Glioma |
| title | Tailored biomimetic nanoreactor improves glioma chemodynamic treatment via triple glutathione depletion and prompt acidity elevation |
| title_full | Tailored biomimetic nanoreactor improves glioma chemodynamic treatment via triple glutathione depletion and prompt acidity elevation |
| title_fullStr | Tailored biomimetic nanoreactor improves glioma chemodynamic treatment via triple glutathione depletion and prompt acidity elevation |
| title_full_unstemmed | Tailored biomimetic nanoreactor improves glioma chemodynamic treatment via triple glutathione depletion and prompt acidity elevation |
| title_short | Tailored biomimetic nanoreactor improves glioma chemodynamic treatment via triple glutathione depletion and prompt acidity elevation |
| title_sort | tailored biomimetic nanoreactor improves glioma chemodynamic treatment via triple glutathione depletion and prompt acidity elevation |
| topic | Biomimetic nanoreactor GSH exhaustion Acidity elevation Chemodynamic therapy Glioma |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425000055 |
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