Breaking the siege of hypoxia and lactate: carrier-free flexible dual-enzyme protein vesicle to ignite photodynamic-immune storm in head and neck squamous cell carcinoma
Photodynamic therapy (PDT) efficacy in head and neck squamous cell carcinoma (HNSCC) is hindered by hypoxia and lactate accumulation in tumor microenvironment (TME), which suppress reactive oxygen species (ROS) generation and immune activation. To address this, we developed a carrier-free flexible d...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-08-01
|
| Series: | Materials Today Bio |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425006520 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850098109801037824 |
|---|---|
| author | Yan Zhou Xiaoquan Xu Ziyue Zu Shangyu Lu Wei Lu Xi Luo Nan Zhong Yang Liu Zhaogang Teng Shouju Wang Feiyun Wu |
| author_facet | Yan Zhou Xiaoquan Xu Ziyue Zu Shangyu Lu Wei Lu Xi Luo Nan Zhong Yang Liu Zhaogang Teng Shouju Wang Feiyun Wu |
| author_sort | Yan Zhou |
| collection | DOAJ |
| description | Photodynamic therapy (PDT) efficacy in head and neck squamous cell carcinoma (HNSCC) is hindered by hypoxia and lactate accumulation in tumor microenvironment (TME), which suppress reactive oxygen species (ROS) generation and immune activation. To address this, we developed a carrier-free flexible dual-enzyme protein vesicle by covalently conjugating human serum albumin (HSA), catalase (CAT), and lactate oxidase (LOX) onto a mesoporous silica template, followed by template etching. Subsequently, the near-infrared photosensitizer IR808 was incorporated to obtain the final nanoparticle (HSA/CAT/LOX@IR808). This system employs a self-sustaining enzymatic cascade: CAT alleviates hypoxia by converting tumor-derived H2O2 into oxygen, while LOX depletes lactate and generates additional H2O2 to fuel CAT activity, synergistically amplifying ROS production. The flexible structure enhances tumor penetration of the nanoparticle, and the incorporation of HSA further enhances endothelial cell transport. In vitro and in vivo studies demonstrated the excellent biocompatibility, tumor-targeting capability, and TME remodeling effects of the vesicle. The vesicle triggered robust immune activation, characterized by M1 macrophage polarization, dendritic cell maturation, and CD8+ T cell infiltration. Ultimately, HSA/CAT/LOX@IR808-mediated PDT led to marked tumor inhibition, prolonged survival, and reduced metastasis. These findings underscore the potential of our protein vesicle as an effective and safe therapeutic approach for HNSCC. |
| format | Article |
| id | doaj-art-1f016b1307fb4bd5a40f7bd6a4281bd9 |
| institution | DOAJ |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-1f016b1307fb4bd5a40f7bd6a4281bd92025-08-20T02:40:48ZengElsevierMaterials Today Bio2590-00642025-08-013310208210.1016/j.mtbio.2025.102082Breaking the siege of hypoxia and lactate: carrier-free flexible dual-enzyme protein vesicle to ignite photodynamic-immune storm in head and neck squamous cell carcinomaYan Zhou0Xiaoquan Xu1Ziyue Zu2Shangyu Lu3Wei Lu4Xi Luo5Nan Zhong6Yang Liu7Zhaogang Teng8Shouju Wang9Feiyun Wu10Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, PR ChinaLaboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, PR China; Corresponding author.Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, PR ChinaLaboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, PR ChinaKey Laboratory for Organic Electronics and Information Displays and Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials, Jiangsu National Synergetic Innovation Centre for Advanced Materials, Nanjing University of Posts and Telecommunications, PR ChinaLaboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, PR ChinaLaboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, PR ChinaLaboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, PR ChinaKey Laboratory for Organic Electronics and Information Displays and Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials, Jiangsu National Synergetic Innovation Centre for Advanced Materials, Nanjing University of Posts and Telecommunications, PR China; Corresponding author. Key Laboratory for Organic Electronics and Information Displays and Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials, Jiangsu National Synergetic Innovation Centre for Advanced Materials, Nanjing University of Posts and Telecommunications, No. 9, Wenyuan Rd, Qixia District, Nanjing, EXT: 210023, PR China.Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, PR China; Corresponding author. Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, No. 300, Guangzhou Rd, Gulou District, Nanjing, EXT210029, PR China.Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, PR China; Corresponding author. Laboratory of Molecular Imaging, Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, No. 300, Guangzhou Rd, Gulou District, Nanjing, EXT210029, PR China.Photodynamic therapy (PDT) efficacy in head and neck squamous cell carcinoma (HNSCC) is hindered by hypoxia and lactate accumulation in tumor microenvironment (TME), which suppress reactive oxygen species (ROS) generation and immune activation. To address this, we developed a carrier-free flexible dual-enzyme protein vesicle by covalently conjugating human serum albumin (HSA), catalase (CAT), and lactate oxidase (LOX) onto a mesoporous silica template, followed by template etching. Subsequently, the near-infrared photosensitizer IR808 was incorporated to obtain the final nanoparticle (HSA/CAT/LOX@IR808). This system employs a self-sustaining enzymatic cascade: CAT alleviates hypoxia by converting tumor-derived H2O2 into oxygen, while LOX depletes lactate and generates additional H2O2 to fuel CAT activity, synergistically amplifying ROS production. The flexible structure enhances tumor penetration of the nanoparticle, and the incorporation of HSA further enhances endothelial cell transport. In vitro and in vivo studies demonstrated the excellent biocompatibility, tumor-targeting capability, and TME remodeling effects of the vesicle. The vesicle triggered robust immune activation, characterized by M1 macrophage polarization, dendritic cell maturation, and CD8+ T cell infiltration. Ultimately, HSA/CAT/LOX@IR808-mediated PDT led to marked tumor inhibition, prolonged survival, and reduced metastasis. These findings underscore the potential of our protein vesicle as an effective and safe therapeutic approach for HNSCC.http://www.sciencedirect.com/science/article/pii/S2590006425006520Head and neck squamous cell carcinomaHypoxiaLactic acidProtein vesiclePhotodynamic therapy |
| spellingShingle | Yan Zhou Xiaoquan Xu Ziyue Zu Shangyu Lu Wei Lu Xi Luo Nan Zhong Yang Liu Zhaogang Teng Shouju Wang Feiyun Wu Breaking the siege of hypoxia and lactate: carrier-free flexible dual-enzyme protein vesicle to ignite photodynamic-immune storm in head and neck squamous cell carcinoma Materials Today Bio Head and neck squamous cell carcinoma Hypoxia Lactic acid Protein vesicle Photodynamic therapy |
| title | Breaking the siege of hypoxia and lactate: carrier-free flexible dual-enzyme protein vesicle to ignite photodynamic-immune storm in head and neck squamous cell carcinoma |
| title_full | Breaking the siege of hypoxia and lactate: carrier-free flexible dual-enzyme protein vesicle to ignite photodynamic-immune storm in head and neck squamous cell carcinoma |
| title_fullStr | Breaking the siege of hypoxia and lactate: carrier-free flexible dual-enzyme protein vesicle to ignite photodynamic-immune storm in head and neck squamous cell carcinoma |
| title_full_unstemmed | Breaking the siege of hypoxia and lactate: carrier-free flexible dual-enzyme protein vesicle to ignite photodynamic-immune storm in head and neck squamous cell carcinoma |
| title_short | Breaking the siege of hypoxia and lactate: carrier-free flexible dual-enzyme protein vesicle to ignite photodynamic-immune storm in head and neck squamous cell carcinoma |
| title_sort | breaking the siege of hypoxia and lactate carrier free flexible dual enzyme protein vesicle to ignite photodynamic immune storm in head and neck squamous cell carcinoma |
| topic | Head and neck squamous cell carcinoma Hypoxia Lactic acid Protein vesicle Photodynamic therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425006520 |
| work_keys_str_mv | AT yanzhou breakingthesiegeofhypoxiaandlactatecarrierfreeflexibledualenzymeproteinvesicletoignitephotodynamicimmunestorminheadandnecksquamouscellcarcinoma AT xiaoquanxu breakingthesiegeofhypoxiaandlactatecarrierfreeflexibledualenzymeproteinvesicletoignitephotodynamicimmunestorminheadandnecksquamouscellcarcinoma AT ziyuezu breakingthesiegeofhypoxiaandlactatecarrierfreeflexibledualenzymeproteinvesicletoignitephotodynamicimmunestorminheadandnecksquamouscellcarcinoma AT shangyulu breakingthesiegeofhypoxiaandlactatecarrierfreeflexibledualenzymeproteinvesicletoignitephotodynamicimmunestorminheadandnecksquamouscellcarcinoma AT weilu breakingthesiegeofhypoxiaandlactatecarrierfreeflexibledualenzymeproteinvesicletoignitephotodynamicimmunestorminheadandnecksquamouscellcarcinoma AT xiluo breakingthesiegeofhypoxiaandlactatecarrierfreeflexibledualenzymeproteinvesicletoignitephotodynamicimmunestorminheadandnecksquamouscellcarcinoma AT nanzhong breakingthesiegeofhypoxiaandlactatecarrierfreeflexibledualenzymeproteinvesicletoignitephotodynamicimmunestorminheadandnecksquamouscellcarcinoma AT yangliu breakingthesiegeofhypoxiaandlactatecarrierfreeflexibledualenzymeproteinvesicletoignitephotodynamicimmunestorminheadandnecksquamouscellcarcinoma AT zhaogangteng breakingthesiegeofhypoxiaandlactatecarrierfreeflexibledualenzymeproteinvesicletoignitephotodynamicimmunestorminheadandnecksquamouscellcarcinoma AT shoujuwang breakingthesiegeofhypoxiaandlactatecarrierfreeflexibledualenzymeproteinvesicletoignitephotodynamicimmunestorminheadandnecksquamouscellcarcinoma AT feiyunwu breakingthesiegeofhypoxiaandlactatecarrierfreeflexibledualenzymeproteinvesicletoignitephotodynamicimmunestorminheadandnecksquamouscellcarcinoma |