Injectable Autocatalytic Hydrogel Triggers Pyroptosis to Stimulate Anticancer Immune Response for Preventing Postoperative Tumor Recurrence
Abstract Modulating immunosuppression while eliminating residual microscopic tumors is critical for inhibiting the postoperative recurrence of triple‐negative breast cancer (TNBC). Although immunotherapy has shown potential in achieving this goal, due to multiple immunosuppression and poor immunogen...
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Wiley
2025-01-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408415 |
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| author | Zhiping Rao Yutong Zhu Zhuang Chen Yi Luo Zuo Yang Weijing Liu Chaoqiang Qiao Yuqiong Xia Peng Yang Dong‐Man Ye Zhongliang Wang |
| author_facet | Zhiping Rao Yutong Zhu Zhuang Chen Yi Luo Zuo Yang Weijing Liu Chaoqiang Qiao Yuqiong Xia Peng Yang Dong‐Man Ye Zhongliang Wang |
| author_sort | Zhiping Rao |
| collection | DOAJ |
| description | Abstract Modulating immunosuppression while eliminating residual microscopic tumors is critical for inhibiting the postoperative recurrence of triple‐negative breast cancer (TNBC). Although immunotherapy has shown potential in achieving this goal, due to multiple immunosuppression and poor immunogenicity of apoptosis, a satisfactory anti‐recurrence effect still faces the challenge. Herein, an injectable hydrogel‐encapsulated autocatalytic copper peroxide (CP@Gel) therapeutic platform is designed and combine it with the clinical‐grade DNA methyltransferase inhibitor decitabine (DAC) to effectively inhibit TNBC growth and postoperative recurrence via pyroptosis, killing residual cancer cells that bypass apoptosis resistance while also improving immunogenicity and modulating immunosuppression to achieve an intense anti‐tumor immune response. Following injection of the CP@Gel, the sustained release of CP leads to the autocatalytic generation of reactive oxygen species, resulting in caspase‐3 activation, and the pre‐administered DAC inhibits the methylation of Gsdme to elevate the GSDME protein levels, leading to intense pyroptosis and anti‐tumor immune responses. The in vivo results show a 67% elimination of local tumor recurrence via treatment with DAC+CP@Gel, suggesting the successful integration of sustained drug release with autocatalysis and epigenetic modification. The results thus suggest great potential for pyroptosis‐based and injectable hydrogel‐aided strategies for preventing the postoperative recurrence of TNBC. |
| format | Article |
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| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-ecab695783d540ada3458410bfb84f4b2025-01-09T11:44:45ZengWileyAdvanced Science2198-38442025-01-01121n/an/a10.1002/advs.202408415Injectable Autocatalytic Hydrogel Triggers Pyroptosis to Stimulate Anticancer Immune Response for Preventing Postoperative Tumor RecurrenceZhiping Rao0Yutong Zhu1Zhuang Chen2Yi Luo3Zuo Yang4Weijing Liu5Chaoqiang Qiao6Yuqiong Xia7Peng Yang8Dong‐Man Ye9Zhongliang Wang10Lab of Molecular Imaging and Translational Medicine (MITM) Engineering Research Center of Molecular & Neuroimaging Ministry of Education School of Life Science and Technology Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment Xi'an Shaanxi 710126 P. R. ChinaLab of Molecular Imaging and Translational Medicine (MITM) Engineering Research Center of Molecular & Neuroimaging Ministry of Education School of Life Science and Technology Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment Xi'an Shaanxi 710126 P. R. ChinaLab of Molecular Imaging and Translational Medicine (MITM) Engineering Research Center of Molecular & Neuroimaging Ministry of Education School of Life Science and Technology Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment Xi'an Shaanxi 710126 P. R. ChinaLab of Molecular Imaging and Translational Medicine (MITM) Engineering Research Center of Molecular & Neuroimaging Ministry of Education School of Life Science and Technology Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment Xi'an Shaanxi 710126 P. R. ChinaLab of Molecular Imaging and Translational Medicine (MITM) Engineering Research Center of Molecular & Neuroimaging Ministry of Education School of Life Science and Technology Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment Xi'an Shaanxi 710126 P. R. ChinaLab of Molecular Imaging and Translational Medicine (MITM) Engineering Research Center of Molecular & Neuroimaging Ministry of Education School of Life Science and Technology Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment Xi'an Shaanxi 710126 P. R. ChinaLab of Molecular Imaging and Translational Medicine (MITM) Engineering Research Center of Molecular & Neuroimaging Ministry of Education School of Life Science and Technology Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment Xi'an Shaanxi 710126 P. R. ChinaLab of Molecular Imaging and Translational Medicine (MITM) Engineering Research Center of Molecular & Neuroimaging Ministry of Education School of Life Science and Technology Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment Xi'an Shaanxi 710126 P. R. ChinaLab of Molecular Imaging and Translational Medicine (MITM) Engineering Research Center of Molecular & Neuroimaging Ministry of Education School of Life Science and Technology Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment Xi'an Shaanxi 710126 P. R. ChinaDepartment of Medical Imaging Cancer Hospital of China Medical University Liaoning Cancer Hospital & Institute Shenyang Liaoning 110042 P. R. ChinaLab of Molecular Imaging and Translational Medicine (MITM) Engineering Research Center of Molecular & Neuroimaging Ministry of Education School of Life Science and Technology Xidian University & International Joint Research Center for Advanced Medical Imaging and Intelligent Diagnosis and Treatment Xi'an Shaanxi 710126 P. R. ChinaAbstract Modulating immunosuppression while eliminating residual microscopic tumors is critical for inhibiting the postoperative recurrence of triple‐negative breast cancer (TNBC). Although immunotherapy has shown potential in achieving this goal, due to multiple immunosuppression and poor immunogenicity of apoptosis, a satisfactory anti‐recurrence effect still faces the challenge. Herein, an injectable hydrogel‐encapsulated autocatalytic copper peroxide (CP@Gel) therapeutic platform is designed and combine it with the clinical‐grade DNA methyltransferase inhibitor decitabine (DAC) to effectively inhibit TNBC growth and postoperative recurrence via pyroptosis, killing residual cancer cells that bypass apoptosis resistance while also improving immunogenicity and modulating immunosuppression to achieve an intense anti‐tumor immune response. Following injection of the CP@Gel, the sustained release of CP leads to the autocatalytic generation of reactive oxygen species, resulting in caspase‐3 activation, and the pre‐administered DAC inhibits the methylation of Gsdme to elevate the GSDME protein levels, leading to intense pyroptosis and anti‐tumor immune responses. The in vivo results show a 67% elimination of local tumor recurrence via treatment with DAC+CP@Gel, suggesting the successful integration of sustained drug release with autocatalysis and epigenetic modification. The results thus suggest great potential for pyroptosis‐based and injectable hydrogel‐aided strategies for preventing the postoperative recurrence of TNBC.https://doi.org/10.1002/advs.202408415hydrogelimmune responsepostsurgical recurrencepyroptosistriple‐negative breast cancer |
| spellingShingle | Zhiping Rao Yutong Zhu Zhuang Chen Yi Luo Zuo Yang Weijing Liu Chaoqiang Qiao Yuqiong Xia Peng Yang Dong‐Man Ye Zhongliang Wang Injectable Autocatalytic Hydrogel Triggers Pyroptosis to Stimulate Anticancer Immune Response for Preventing Postoperative Tumor Recurrence Advanced Science hydrogel immune response postsurgical recurrence pyroptosis triple‐negative breast cancer |
| title | Injectable Autocatalytic Hydrogel Triggers Pyroptosis to Stimulate Anticancer Immune Response for Preventing Postoperative Tumor Recurrence |
| title_full | Injectable Autocatalytic Hydrogel Triggers Pyroptosis to Stimulate Anticancer Immune Response for Preventing Postoperative Tumor Recurrence |
| title_fullStr | Injectable Autocatalytic Hydrogel Triggers Pyroptosis to Stimulate Anticancer Immune Response for Preventing Postoperative Tumor Recurrence |
| title_full_unstemmed | Injectable Autocatalytic Hydrogel Triggers Pyroptosis to Stimulate Anticancer Immune Response for Preventing Postoperative Tumor Recurrence |
| title_short | Injectable Autocatalytic Hydrogel Triggers Pyroptosis to Stimulate Anticancer Immune Response for Preventing Postoperative Tumor Recurrence |
| title_sort | injectable autocatalytic hydrogel triggers pyroptosis to stimulate anticancer immune response for preventing postoperative tumor recurrence |
| topic | hydrogel immune response postsurgical recurrence pyroptosis triple‐negative breast cancer |
| url | https://doi.org/10.1002/advs.202408415 |
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