Self‐Cooperative Prodrug Nanovesicles Migrate Immune Evasion to Potentiate Chemoradiotherapy in Head and Neck Cancer
Abstract Chemoradiotherapy is the standard of care for the clinical treatment of locally advanced head and neck cancers. However, the combination of ion radiation with free chemotherapeutics yields unsatisfactory therapeutic output and severe side effects due to the nonspecific biodistribution of th...
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| Format: | Article |
| Language: | English |
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Wiley
2022-12-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202203263 |
| _version_ | 1797975010491498496 |
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| author | Yun Zhu Shunan Zhang Yi Lai Jiaxing Pan Fangmin Chen Tingting Wang Fengyang Wang Zhiai Xu Wenjun Yang Haijun Yu |
| author_facet | Yun Zhu Shunan Zhang Yi Lai Jiaxing Pan Fangmin Chen Tingting Wang Fengyang Wang Zhiai Xu Wenjun Yang Haijun Yu |
| author_sort | Yun Zhu |
| collection | DOAJ |
| description | Abstract Chemoradiotherapy is the standard of care for the clinical treatment of locally advanced head and neck cancers. However, the combination of ion radiation with free chemotherapeutics yields unsatisfactory therapeutic output and severe side effects due to the nonspecific biodistribution of the anticancer drugs. Herein, a self‐cooperative prodrug nanovesicle is reported for highly tumor‐specific chemoradiotherapy. The nanovesicles integrating a prodrug of oxaliplatin (OXA) can passively accumulate at the tumor site and penetrate deep into the tumor mass via matrix metalloproteinase 2‐mediated cleavage of the polyethylene glycol corona. The OXA prodrug can be restored inside the tumor cells with endogenous glutathione to trigger immunogenic cell death (ICD) of the tumor cells and sensitize the tumor to ion radiation. The nanovesicles can be further loaded with the JAK inhibitor ruxolitinib to abolish chemoradiotherapy‐induced programmed death ligand 1 (PD‐L1) upregulation on the surface of the tumor cells, thereby prompting chemoradiotherapy‐induced immunotherapy by blocking the interferon gamma‐Janus kinase‐signal transducer and activator of transcription axis. The prodrug nanoplatform reported herein might present a novel strategy to cooperatively enhance chemoradiotherapy of head and cancer and overcome PD‐L1‐dependent immune evasion. |
| first_indexed | 2024-04-11T04:28:50Z |
| format | Article |
| id | doaj.art-ff5357cb5dc24c7ba8cb52ecfbccd23b |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-11T04:28:50Z |
| publishDate | 2022-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-ff5357cb5dc24c7ba8cb52ecfbccd23b2022-12-29T14:19:16ZengWileyAdvanced Science2198-38442022-12-01936n/an/a10.1002/advs.202203263Self‐Cooperative Prodrug Nanovesicles Migrate Immune Evasion to Potentiate Chemoradiotherapy in Head and Neck CancerYun Zhu0Shunan Zhang1Yi Lai2Jiaxing Pan3Fangmin Chen4Tingting Wang5Fengyang Wang6Zhiai Xu7Wenjun Yang8Haijun Yu9Department of Oral and Maxillofacial‐Head and Neck Oncology Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai 200011 ChinaCenter of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaCenter of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaCenter of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaCenter of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaDepartment of Medical Ultrasound Shanghai Tenth People's Hospital; Tongji University Shanghai 200072 ChinaDepartment of Medical Ultrasound Shanghai Tenth People's Hospital; Tongji University Shanghai 200072 ChinaSchool of Chemistry and Molecular Engineering East China Normal University Shanghai 200241 ChinaDepartment of Oral and Maxillofacial‐Head and Neck Oncology Ninth People's Hospital College of Stomatology Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases Shanghai Key Laboratory of Stomatology Shanghai 200011 ChinaCenter of Pharmaceutics Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai 201203 ChinaAbstract Chemoradiotherapy is the standard of care for the clinical treatment of locally advanced head and neck cancers. However, the combination of ion radiation with free chemotherapeutics yields unsatisfactory therapeutic output and severe side effects due to the nonspecific biodistribution of the anticancer drugs. Herein, a self‐cooperative prodrug nanovesicle is reported for highly tumor‐specific chemoradiotherapy. The nanovesicles integrating a prodrug of oxaliplatin (OXA) can passively accumulate at the tumor site and penetrate deep into the tumor mass via matrix metalloproteinase 2‐mediated cleavage of the polyethylene glycol corona. The OXA prodrug can be restored inside the tumor cells with endogenous glutathione to trigger immunogenic cell death (ICD) of the tumor cells and sensitize the tumor to ion radiation. The nanovesicles can be further loaded with the JAK inhibitor ruxolitinib to abolish chemoradiotherapy‐induced programmed death ligand 1 (PD‐L1) upregulation on the surface of the tumor cells, thereby prompting chemoradiotherapy‐induced immunotherapy by blocking the interferon gamma‐Janus kinase‐signal transducer and activator of transcription axis. The prodrug nanoplatform reported herein might present a novel strategy to cooperatively enhance chemoradiotherapy of head and cancer and overcome PD‐L1‐dependent immune evasion.https://doi.org/10.1002/advs.202203263chemoradiotherapycooperative therapyhead and neck cancerimmune evasionimmunogenic cell death |
| spellingShingle | Yun Zhu Shunan Zhang Yi Lai Jiaxing Pan Fangmin Chen Tingting Wang Fengyang Wang Zhiai Xu Wenjun Yang Haijun Yu Self‐Cooperative Prodrug Nanovesicles Migrate Immune Evasion to Potentiate Chemoradiotherapy in Head and Neck Cancer Advanced Science chemoradiotherapy cooperative therapy head and neck cancer immune evasion immunogenic cell death |
| title | Self‐Cooperative Prodrug Nanovesicles Migrate Immune Evasion to Potentiate Chemoradiotherapy in Head and Neck Cancer |
| title_full | Self‐Cooperative Prodrug Nanovesicles Migrate Immune Evasion to Potentiate Chemoradiotherapy in Head and Neck Cancer |
| title_fullStr | Self‐Cooperative Prodrug Nanovesicles Migrate Immune Evasion to Potentiate Chemoradiotherapy in Head and Neck Cancer |
| title_full_unstemmed | Self‐Cooperative Prodrug Nanovesicles Migrate Immune Evasion to Potentiate Chemoradiotherapy in Head and Neck Cancer |
| title_short | Self‐Cooperative Prodrug Nanovesicles Migrate Immune Evasion to Potentiate Chemoradiotherapy in Head and Neck Cancer |
| title_sort | self cooperative prodrug nanovesicles migrate immune evasion to potentiate chemoradiotherapy in head and neck cancer |
| topic | chemoradiotherapy cooperative therapy head and neck cancer immune evasion immunogenic cell death |
| url | https://doi.org/10.1002/advs.202203263 |
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