Biodegradable Materials with Disulfide-Bridged-Framework Confine Photosensitizers for Enhanced Photo-Immunotherapy
Dongbei Li,1 Fangman Chen,2 Cheng Cheng,1 Haijun Li,3,* Xudong Wei1,* 1Department of Hematology, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou City, Henan Province, People’s Republic of China; 2School of Biomedical Engineering (Suzhou), Division...
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| Format: | Article |
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Dove Medical Press
2021-12-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/biodegradable-materials-with-disulfide-bridged-framework-confine-photo-peer-reviewed-fulltext-article-IJN |
| _version_ | 1819001730672623616 |
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| author | Li D Chen F Cheng C Li H Wei X |
| author_facet | Li D Chen F Cheng C Li H Wei X |
| author_sort | Li D |
| collection | DOAJ |
| description | Dongbei Li,1 Fangman Chen,2 Cheng Cheng,1 Haijun Li,3,* Xudong Wei1,* 1Department of Hematology, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou City, Henan Province, People’s Republic of China; 2School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xudong Wei; Haijun Li Email xudongwei@zzu.edu.cn; navylizz@sina.comPurpose: Photodynamic therapy (PDT) with spatiotemporal controlled and noninvasive advantages has obtained growing attention in cancer treatment. Nevertheless, PDT still suffers from self-aggregation-induced photosensitizer quenching and reactive oxygen species (ROS) scavenging in cancer cells with abundant glutathione (GSH) pools, leading to insufficient performance.Methods: In this study, we develop a versatile nanocarrier (SSNs) with a disulfide-bond-bridged silica framework for enhanced photo-immunotherapy. Such SSNs spatially confine photosensitizers Ce6 in the matrix to prevent self-aggregation. Under the high GSH level of cancer cells, the disulfide-bond-bridged framework was degradable and triggered the exposure of photosensitizers to oxygen, accelerating the ROS generation during PDT. In addition, GSH depletion via the break of the disulfide-bond increased the ROS level, together resulting in efficient tumor killing outcomes with a considerable immunogenic cell death effect in vitro. Importantly, the SSNs@Ce6 accumulated in the tumor site and exhibited enhanced PDT efficacy with low systemic toxicity in vivo.Results: The GEN-loaded nanoplatform (Ag-MONs@GEN) showed glutathione-responsive matrix degradation, resulting in the simultaneous controlled release of GEN and silver ions. Ag-MONs@GEN exhibited excellent anti-bacterial activities than Ag-MONs and GEN alone, especially enhancing synergetic effects against four antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Moreover, Ag-MONs@GEN showed good biocompatibility on L929 and HUVECS.Conclusion: Notably, SSNs@Ce6-mediated PDT completely eradicated 4T1 tumors when combined with the PD-1 checkpoint blockade. Overall, the confinement of photosensitizers in a biodegradable disulfide-bridged-framework provides a promising strategy to unleash the potential of photosensitizers in PDT, especially in combined cancer photo-immunotherapy.Keywords: photodynamic therapy, glutathione depletion, photosensitizer confinement, degradation, cancer immunotherapy |
| first_indexed | 2024-12-20T22:53:52Z |
| format | Article |
| id | doaj.art-36a0273c44de4887bef29073e7f0440c |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-12-20T22:53:52Z |
| publishDate | 2021-12-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-36a0273c44de4887bef29073e7f0440c2022-12-21T19:24:09ZengDove Medical PressInternational Journal of Nanomedicine1178-20132021-12-01Volume 168323833471801Biodegradable Materials with Disulfide-Bridged-Framework Confine Photosensitizers for Enhanced Photo-ImmunotherapyLi DChen FCheng CLi HWei XDongbei Li,1 Fangman Chen,2 Cheng Cheng,1 Haijun Li,3,* Xudong Wei1,* 1Department of Hematology, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou City, Henan Province, People’s Republic of China; 2School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230026, People’s Republic of China; 3Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xudong Wei; Haijun Li Email xudongwei@zzu.edu.cn; navylizz@sina.comPurpose: Photodynamic therapy (PDT) with spatiotemporal controlled and noninvasive advantages has obtained growing attention in cancer treatment. Nevertheless, PDT still suffers from self-aggregation-induced photosensitizer quenching and reactive oxygen species (ROS) scavenging in cancer cells with abundant glutathione (GSH) pools, leading to insufficient performance.Methods: In this study, we develop a versatile nanocarrier (SSNs) with a disulfide-bond-bridged silica framework for enhanced photo-immunotherapy. Such SSNs spatially confine photosensitizers Ce6 in the matrix to prevent self-aggregation. Under the high GSH level of cancer cells, the disulfide-bond-bridged framework was degradable and triggered the exposure of photosensitizers to oxygen, accelerating the ROS generation during PDT. In addition, GSH depletion via the break of the disulfide-bond increased the ROS level, together resulting in efficient tumor killing outcomes with a considerable immunogenic cell death effect in vitro. Importantly, the SSNs@Ce6 accumulated in the tumor site and exhibited enhanced PDT efficacy with low systemic toxicity in vivo.Results: The GEN-loaded nanoplatform (Ag-MONs@GEN) showed glutathione-responsive matrix degradation, resulting in the simultaneous controlled release of GEN and silver ions. Ag-MONs@GEN exhibited excellent anti-bacterial activities than Ag-MONs and GEN alone, especially enhancing synergetic effects against four antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Moreover, Ag-MONs@GEN showed good biocompatibility on L929 and HUVECS.Conclusion: Notably, SSNs@Ce6-mediated PDT completely eradicated 4T1 tumors when combined with the PD-1 checkpoint blockade. Overall, the confinement of photosensitizers in a biodegradable disulfide-bridged-framework provides a promising strategy to unleash the potential of photosensitizers in PDT, especially in combined cancer photo-immunotherapy.Keywords: photodynamic therapy, glutathione depletion, photosensitizer confinement, degradation, cancer immunotherapyhttps://www.dovepress.com/biodegradable-materials-with-disulfide-bridged-framework-confine-photo-peer-reviewed-fulltext-article-IJNphotodynamic therapyglutathione depletionphotosensitizer confinementdegradationcancer immunotherapy |
| spellingShingle | Li D Chen F Cheng C Li H Wei X Biodegradable Materials with Disulfide-Bridged-Framework Confine Photosensitizers for Enhanced Photo-Immunotherapy International Journal of Nanomedicine photodynamic therapy glutathione depletion photosensitizer confinement degradation cancer immunotherapy |
| title | Biodegradable Materials with Disulfide-Bridged-Framework Confine Photosensitizers for Enhanced Photo-Immunotherapy |
| title_full | Biodegradable Materials with Disulfide-Bridged-Framework Confine Photosensitizers for Enhanced Photo-Immunotherapy |
| title_fullStr | Biodegradable Materials with Disulfide-Bridged-Framework Confine Photosensitizers for Enhanced Photo-Immunotherapy |
| title_full_unstemmed | Biodegradable Materials with Disulfide-Bridged-Framework Confine Photosensitizers for Enhanced Photo-Immunotherapy |
| title_short | Biodegradable Materials with Disulfide-Bridged-Framework Confine Photosensitizers for Enhanced Photo-Immunotherapy |
| title_sort | biodegradable materials with disulfide bridged framework confine photosensitizers for enhanced photo immunotherapy |
| topic | photodynamic therapy glutathione depletion photosensitizer confinement degradation cancer immunotherapy |
| url | https://www.dovepress.com/biodegradable-materials-with-disulfide-bridged-framework-confine-photo-peer-reviewed-fulltext-article-IJN |
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