An Anisotropic Gold‐Palladium Heterostructured Nanosystem for Synergistically Overcoming Radioresistance and Enhancing Melanoma Radioimmunotherapy
Abstract Radiotherapy (RT) has recently reemerged as a promising approach for melanoma treatment because of its potential to trigger abscopal effects. However, the intrinsic radioresistance of melanoma significantly diminishes RT‐induced DNA damage and the subsequent release of immunostimulatory mol...
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Wiley
2025-08-01
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| Online Access: | https://doi.org/10.1002/advs.202500492 |
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| author | Cheng Chen Yuqi Huang Wandong Wang Minghao Chao Weiguo Sun Yinghui Kong Guan Jiang Yong Gao Fenglei Gao |
| author_facet | Cheng Chen Yuqi Huang Wandong Wang Minghao Chao Weiguo Sun Yinghui Kong Guan Jiang Yong Gao Fenglei Gao |
| author_sort | Cheng Chen |
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| description | Abstract Radiotherapy (RT) has recently reemerged as a promising approach for melanoma treatment because of its potential to trigger abscopal effects. However, the intrinsic radioresistance of melanoma significantly diminishes RT‐induced DNA damage and the subsequent release of immunostimulatory molecules, thereby impairing systemic antitumor immunity. To overcome these challenges, a multifunctional anisotropic Au‐Pd heterostructured nanosystem (APSMR) is developed that incorporates a plasmonically enhanced Au‐Pd core, with a shell composed of a biodegradable, Mn‐doped targeting peptide. The nanosystem integrates photothermal, radiotherapeutic, and immunomodulatory functions. Under 1064 nm laser irradiation, APSMR generates reactive oxygen species (ROS) via plasmon‐driven catalysis and Mn‐mediated Fenton‐like reactions. Concurrently, mild hyperthermia (HT) promotes oxygenation and disrupts DNA repair pathways, resulting in multi‐directional DNA damage and an increase in immunogenic cell death (ICD). Furthermore, the release of Mn2⁺ ions activates the cGAS–STING pathway, which synergizes with ICD to promote systemic antitumor immunity. Notably, APSMR treatment also upregulates PD‐L1 expression, thereby sensitizing tumors to immune checkpoint blockade. Collectively, APSMR offers a potent and synergistic strategy to amplify RT‐driven tumor vaccination and improve therapeutic responses against metastatic melanoma. |
| format | Article |
| id | doaj-art-664b3347ebec47bb80ee6907812e8b9c |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
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| spelling | doaj-art-664b3347ebec47bb80ee6907812e8b9c2025-08-23T14:14:38ZengWileyAdvanced Science2198-38442025-08-011231n/an/a10.1002/advs.202500492An Anisotropic Gold‐Palladium Heterostructured Nanosystem for Synergistically Overcoming Radioresistance and Enhancing Melanoma RadioimmunotherapyCheng Chen0Yuqi Huang1Wandong Wang2Minghao Chao3Weiguo Sun4Yinghui Kong5Guan Jiang6Yong Gao7Fenglei Gao8Department of Dermatology The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University Jiangsu 223300 P. R. ChinaDepartment of Dermatology The Affiliated Suzhou Hospital of Nanjing Medical University Jiangsu 215000 P. R. ChinaJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Jiangsu 221004 P. R. ChinaJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Jiangsu 221004 P. R. ChinaDepartment of Dermatology The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University Jiangsu 223300 P. R. ChinaDepartment of Dermatology The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University Jiangsu 223300 P. R. ChinaDepartment of Dermatology Affiliated Hospital of Xuzhou Medical University Xuzhou Jiangsu 221002 P. R. ChinaDepartment of Oncology The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University Jiangsu 223300 P. R. ChinaJiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical University Jiangsu 221004 P. R. ChinaAbstract Radiotherapy (RT) has recently reemerged as a promising approach for melanoma treatment because of its potential to trigger abscopal effects. However, the intrinsic radioresistance of melanoma significantly diminishes RT‐induced DNA damage and the subsequent release of immunostimulatory molecules, thereby impairing systemic antitumor immunity. To overcome these challenges, a multifunctional anisotropic Au‐Pd heterostructured nanosystem (APSMR) is developed that incorporates a plasmonically enhanced Au‐Pd core, with a shell composed of a biodegradable, Mn‐doped targeting peptide. The nanosystem integrates photothermal, radiotherapeutic, and immunomodulatory functions. Under 1064 nm laser irradiation, APSMR generates reactive oxygen species (ROS) via plasmon‐driven catalysis and Mn‐mediated Fenton‐like reactions. Concurrently, mild hyperthermia (HT) promotes oxygenation and disrupts DNA repair pathways, resulting in multi‐directional DNA damage and an increase in immunogenic cell death (ICD). Furthermore, the release of Mn2⁺ ions activates the cGAS–STING pathway, which synergizes with ICD to promote systemic antitumor immunity. Notably, APSMR treatment also upregulates PD‐L1 expression, thereby sensitizing tumors to immune checkpoint blockade. Collectively, APSMR offers a potent and synergistic strategy to amplify RT‐driven tumor vaccination and improve therapeutic responses against metastatic melanoma.https://doi.org/10.1002/advs.202500492melanomamild hyperthermia therapynanovaccineradioimmunotherapy |
| spellingShingle | Cheng Chen Yuqi Huang Wandong Wang Minghao Chao Weiguo Sun Yinghui Kong Guan Jiang Yong Gao Fenglei Gao An Anisotropic Gold‐Palladium Heterostructured Nanosystem for Synergistically Overcoming Radioresistance and Enhancing Melanoma Radioimmunotherapy Advanced Science melanoma mild hyperthermia therapy nanovaccine radioimmunotherapy |
| title | An Anisotropic Gold‐Palladium Heterostructured Nanosystem for Synergistically Overcoming Radioresistance and Enhancing Melanoma Radioimmunotherapy |
| title_full | An Anisotropic Gold‐Palladium Heterostructured Nanosystem for Synergistically Overcoming Radioresistance and Enhancing Melanoma Radioimmunotherapy |
| title_fullStr | An Anisotropic Gold‐Palladium Heterostructured Nanosystem for Synergistically Overcoming Radioresistance and Enhancing Melanoma Radioimmunotherapy |
| title_full_unstemmed | An Anisotropic Gold‐Palladium Heterostructured Nanosystem for Synergistically Overcoming Radioresistance and Enhancing Melanoma Radioimmunotherapy |
| title_short | An Anisotropic Gold‐Palladium Heterostructured Nanosystem for Synergistically Overcoming Radioresistance and Enhancing Melanoma Radioimmunotherapy |
| title_sort | anisotropic gold palladium heterostructured nanosystem for synergistically overcoming radioresistance and enhancing melanoma radioimmunotherapy |
| topic | melanoma mild hyperthermia therapy nanovaccine radioimmunotherapy |
| url | https://doi.org/10.1002/advs.202500492 |
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