Light-controlled pyroptosis via redox-responsive microneedles enhances photodynamic–epigenetic immunotherapy in breast cancer
Despite the potential of photodynamic therapy in breast cancer treatment, inadequate immunogenicity and inefficient pyroptosis induction remain critical limitations. To address this, we developed dissolvable microneedles (MNs) for localized co-delivery of decitabine (DEC) and glutathione (GSH)-respo...
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Elsevier
2025-10-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425007288 |
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| author | Hang Yu Yiqing Chen Jinjin Yin Zhongwen Yuan Senling Feng Yanrong Duan Pengke Yan Shengyao Liu Wenting Zhu |
| author_facet | Hang Yu Yiqing Chen Jinjin Yin Zhongwen Yuan Senling Feng Yanrong Duan Pengke Yan Shengyao Liu Wenting Zhu |
| author_sort | Hang Yu |
| collection | DOAJ |
| description | Despite the potential of photodynamic therapy in breast cancer treatment, inadequate immunogenicity and inefficient pyroptosis induction remain critical limitations. To address this, we developed dissolvable microneedles (MNs) for localized co-delivery of decitabine (DEC) and glutathione (GSH)-responsive photosensitizer nanoparticles (HPPH-ss-NPs), aiming to potentiate immunogenic pyroptosis in breast cancer. The MNs enabled spatiotemporal control of DEC (dissolution-dependent release) and HPPH-ss-NPs (GSH-triggered activation), enhancing tumor drug levels with reduced systemic exposure. Mechanistically, DEC restored pyroptosis executioner gasdermin E (GSDME) expression, while HPPH-ss-NPs depleted intracellular GSH and generated caspase-3-activating ROS under light irradiation. The synergistic action triggered GSDME-dependent pyroptosis, releasing immunostimulatory DAMPs that increased mature dendritic cells and tumor-infiltrating CD8+ T cells. In orthotopic models, (DEC + HPPH-ss-NPs)@MNs suppressed primary tumor growth, while combining with anti-PD-1 synergistically inhibited tumor recurrence and lung metastasis, establishing durable systemic immunity. This MN-based platform establishes a localized photodynamic-epigenetic crosstalk to convert immunologically inert tumors into pyroptosis-driven immunogenic niches, providing a strategy for combinatorial breast cancer therapy. |
| format | Article |
| id | doaj-art-632d0d1c1f404a37a026fa89094cdbbe |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-632d0d1c1f404a37a026fa89094cdbbe2025-08-20T04:00:27ZengElsevierMaterials Today Bio2590-00642025-10-013410215810.1016/j.mtbio.2025.102158Light-controlled pyroptosis via redox-responsive microneedles enhances photodynamic–epigenetic immunotherapy in breast cancerHang Yu0Yiqing Chen1Jinjin Yin2Zhongwen Yuan3Senling Feng4Yanrong Duan5Pengke Yan6Shengyao Liu7Wenting Zhu8Department of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, ChinaDepartment of Neurosurgery and Neurosurgical Disease Research Centre, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510006, ChinaDepartment of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, ChinaDepartment of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, ChinaDepartment of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, ChinaDepartment of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, ChinaDepartment of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China; Corresponding author.Department of Spine Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China; Corresponding author.Department of Pharmacy, Biomedicine Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510150, China; Corresponding author.Despite the potential of photodynamic therapy in breast cancer treatment, inadequate immunogenicity and inefficient pyroptosis induction remain critical limitations. To address this, we developed dissolvable microneedles (MNs) for localized co-delivery of decitabine (DEC) and glutathione (GSH)-responsive photosensitizer nanoparticles (HPPH-ss-NPs), aiming to potentiate immunogenic pyroptosis in breast cancer. The MNs enabled spatiotemporal control of DEC (dissolution-dependent release) and HPPH-ss-NPs (GSH-triggered activation), enhancing tumor drug levels with reduced systemic exposure. Mechanistically, DEC restored pyroptosis executioner gasdermin E (GSDME) expression, while HPPH-ss-NPs depleted intracellular GSH and generated caspase-3-activating ROS under light irradiation. The synergistic action triggered GSDME-dependent pyroptosis, releasing immunostimulatory DAMPs that increased mature dendritic cells and tumor-infiltrating CD8+ T cells. In orthotopic models, (DEC + HPPH-ss-NPs)@MNs suppressed primary tumor growth, while combining with anti-PD-1 synergistically inhibited tumor recurrence and lung metastasis, establishing durable systemic immunity. This MN-based platform establishes a localized photodynamic-epigenetic crosstalk to convert immunologically inert tumors into pyroptosis-driven immunogenic niches, providing a strategy for combinatorial breast cancer therapy.http://www.sciencedirect.com/science/article/pii/S2590006425007288Soluble microneedlePyroptosisPhotodynamic therapyGlutathione depletionBreast cancer |
| spellingShingle | Hang Yu Yiqing Chen Jinjin Yin Zhongwen Yuan Senling Feng Yanrong Duan Pengke Yan Shengyao Liu Wenting Zhu Light-controlled pyroptosis via redox-responsive microneedles enhances photodynamic–epigenetic immunotherapy in breast cancer Materials Today Bio Soluble microneedle Pyroptosis Photodynamic therapy Glutathione depletion Breast cancer |
| title | Light-controlled pyroptosis via redox-responsive microneedles enhances photodynamic–epigenetic immunotherapy in breast cancer |
| title_full | Light-controlled pyroptosis via redox-responsive microneedles enhances photodynamic–epigenetic immunotherapy in breast cancer |
| title_fullStr | Light-controlled pyroptosis via redox-responsive microneedles enhances photodynamic–epigenetic immunotherapy in breast cancer |
| title_full_unstemmed | Light-controlled pyroptosis via redox-responsive microneedles enhances photodynamic–epigenetic immunotherapy in breast cancer |
| title_short | Light-controlled pyroptosis via redox-responsive microneedles enhances photodynamic–epigenetic immunotherapy in breast cancer |
| title_sort | light controlled pyroptosis via redox responsive microneedles enhances photodynamic epigenetic immunotherapy in breast cancer |
| topic | Soluble microneedle Pyroptosis Photodynamic therapy Glutathione depletion Breast cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425007288 |
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