Verteporfin‐Mediated In Situ Nanovaccine Based on Local Conventional‐Dose Hypofractionated Radiotherapy Enhances Antitumor and Immunomodulatory Effect
Abstract In situ radiotherapy is the most successful cytotoxic therapy available for the treatment of solid tumors, while high‐dose radiotherapy per fraction is not yet widely and reliably used. To some extent, the major considerations of the disappointing results are on the risk of high‐dose irradi...
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202413387 |
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| author | Zhifan Zhang Lin Li Yuchen Ge Anni Chen Shanchao Diao Yueling Yang Qianyue Chen Yingling Zhou Jie Shao Fanyan Meng Lixia Yu Manman Tian Xiaoping Qian Zhaoyu Lin Chen Xie Baorui Liu Rutian Li |
| author_facet | Zhifan Zhang Lin Li Yuchen Ge Anni Chen Shanchao Diao Yueling Yang Qianyue Chen Yingling Zhou Jie Shao Fanyan Meng Lixia Yu Manman Tian Xiaoping Qian Zhaoyu Lin Chen Xie Baorui Liu Rutian Li |
| author_sort | Zhifan Zhang |
| collection | DOAJ |
| description | Abstract In situ radiotherapy is the most successful cytotoxic therapy available for the treatment of solid tumors, while high‐dose radiotherapy per fraction is not yet widely and reliably used. To some extent, the major considerations of the disappointing results are on the risk of high‐dose irradiation‐induced damage to the surrounding normal tissues and the difficulty in distant metastasis control. To break these restraints, a gelatinase‐responsive amphiphilic methoxypolyethyleneglycol–PVGLIG–polycaprolactone (mPEG–PVGLIG–PCL) nanoparticles’ loading verteporfin (N@VP), a special photosensitizer that can also be excited by X‐rays to produce cytotoxic singlet oxygen and greatly enhance radiotherapy efficacy, is prepared in this study. Herein, it is shown that the formed N@VP combined with conventional‐dose radiation therapy (RT, 2 Gy (gray, a radiation dose unit)) can realize an antitumor effect no less than high‐dose RT (8 Gy) and minimize radiation dose necessary to achieve local tumor control. Moreover, this radiosensitive nanosystem can exert excellent systemic antitumor immunity and abscopal effect, providing a preferable “in situ vaccine” strategy based on conventional‐dose RT to achieve efficient systemic management of distant tumor metastasis. When combined with immunotherapy, this novel strategy for radiosensitization results in better immunotherapy sensitivity by stimulating significant immunogenic tumor cell death and synergistic antitumor immune responses. |
| format | Article |
| id | doaj-art-0f7676d347324d899495daa24afbb5f7 |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-0f7676d347324d899495daa24afbb5f72025-08-20T02:02:16ZengWileyAdvanced Science2198-38442025-05-011220n/an/a10.1002/advs.202413387Verteporfin‐Mediated In Situ Nanovaccine Based on Local Conventional‐Dose Hypofractionated Radiotherapy Enhances Antitumor and Immunomodulatory EffectZhifan Zhang0Lin Li1Yuchen Ge2Anni Chen3Shanchao Diao4Yueling Yang5Qianyue Chen6Yingling Zhou7Jie Shao8Fanyan Meng9Lixia Yu10Manman Tian11Xiaoping Qian12Zhaoyu Lin13Chen Xie14Baorui Liu15Rutian Li16The Comprehensive Cancer Center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210008 ChinaDepartment of Pathology Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210008 ChinaThe Comprehensive Cancer Center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210008 ChinaNanjing International Hospital Medical School of Nanjing University Nanjing 210019 ChinaState Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM) Jiangsu Key Laboratory for Biosensors Nanjing University of Posts & Telecommunications Nanjing 210023 ChinaDepartment of Oncology Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine Nanjing 210008 ChinaState Key Laboratory of Pharmaceutical Biotechnology Ministry of Education Key Laboratory of Model Animal for Disease Study Jiangsu Key Laboratory of Molecular Medicine Model Animal Research Center National Resource Center for Mutant Mice of China Nanjing Drum Tower Hospital School of Medicine Nanjing University Nanjing 210061 ChinaDepartment of Oncology Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine Nanjing University of Chinese Medicine Nanjing 210008 ChinaThe Comprehensive Cancer Center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210008 ChinaThe Comprehensive Cancer Center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210008 ChinaThe Comprehensive Cancer Center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210008 ChinaThe Comprehensive Cancer Center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210008 ChinaThe Comprehensive Cancer Center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210008 ChinaState Key Laboratory of Pharmaceutical Biotechnology Ministry of Education Key Laboratory of Model Animal for Disease Study Jiangsu Key Laboratory of Molecular Medicine Model Animal Research Center National Resource Center for Mutant Mice of China Nanjing Drum Tower Hospital School of Medicine Nanjing University Nanjing 210061 ChinaState Key Laboratory for Organic Electronics and Information Displays & Institute of Advanced Materials (IAM) Jiangsu Key Laboratory for Biosensors Nanjing University of Posts & Telecommunications Nanjing 210023 ChinaThe Comprehensive Cancer Center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210008 ChinaThe Comprehensive Cancer Center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical School Nanjing University Nanjing 210008 ChinaAbstract In situ radiotherapy is the most successful cytotoxic therapy available for the treatment of solid tumors, while high‐dose radiotherapy per fraction is not yet widely and reliably used. To some extent, the major considerations of the disappointing results are on the risk of high‐dose irradiation‐induced damage to the surrounding normal tissues and the difficulty in distant metastasis control. To break these restraints, a gelatinase‐responsive amphiphilic methoxypolyethyleneglycol–PVGLIG–polycaprolactone (mPEG–PVGLIG–PCL) nanoparticles’ loading verteporfin (N@VP), a special photosensitizer that can also be excited by X‐rays to produce cytotoxic singlet oxygen and greatly enhance radiotherapy efficacy, is prepared in this study. Herein, it is shown that the formed N@VP combined with conventional‐dose radiation therapy (RT, 2 Gy (gray, a radiation dose unit)) can realize an antitumor effect no less than high‐dose RT (8 Gy) and minimize radiation dose necessary to achieve local tumor control. Moreover, this radiosensitive nanosystem can exert excellent systemic antitumor immunity and abscopal effect, providing a preferable “in situ vaccine” strategy based on conventional‐dose RT to achieve efficient systemic management of distant tumor metastasis. When combined with immunotherapy, this novel strategy for radiosensitization results in better immunotherapy sensitivity by stimulating significant immunogenic tumor cell death and synergistic antitumor immune responses.https://doi.org/10.1002/advs.202413387hypofractionated radiotherapyimmunomodulatory effectnanovaccinationradiosensitizationtumor‐targeting nanoparticlesverteporfin |
| spellingShingle | Zhifan Zhang Lin Li Yuchen Ge Anni Chen Shanchao Diao Yueling Yang Qianyue Chen Yingling Zhou Jie Shao Fanyan Meng Lixia Yu Manman Tian Xiaoping Qian Zhaoyu Lin Chen Xie Baorui Liu Rutian Li Verteporfin‐Mediated In Situ Nanovaccine Based on Local Conventional‐Dose Hypofractionated Radiotherapy Enhances Antitumor and Immunomodulatory Effect Advanced Science hypofractionated radiotherapy immunomodulatory effect nanovaccination radiosensitization tumor‐targeting nanoparticles verteporfin |
| title | Verteporfin‐Mediated In Situ Nanovaccine Based on Local Conventional‐Dose Hypofractionated Radiotherapy Enhances Antitumor and Immunomodulatory Effect |
| title_full | Verteporfin‐Mediated In Situ Nanovaccine Based on Local Conventional‐Dose Hypofractionated Radiotherapy Enhances Antitumor and Immunomodulatory Effect |
| title_fullStr | Verteporfin‐Mediated In Situ Nanovaccine Based on Local Conventional‐Dose Hypofractionated Radiotherapy Enhances Antitumor and Immunomodulatory Effect |
| title_full_unstemmed | Verteporfin‐Mediated In Situ Nanovaccine Based on Local Conventional‐Dose Hypofractionated Radiotherapy Enhances Antitumor and Immunomodulatory Effect |
| title_short | Verteporfin‐Mediated In Situ Nanovaccine Based on Local Conventional‐Dose Hypofractionated Radiotherapy Enhances Antitumor and Immunomodulatory Effect |
| title_sort | verteporfin mediated in situ nanovaccine based on local conventional dose hypofractionated radiotherapy enhances antitumor and immunomodulatory effect |
| topic | hypofractionated radiotherapy immunomodulatory effect nanovaccination radiosensitization tumor‐targeting nanoparticles verteporfin |
| url | https://doi.org/10.1002/advs.202413387 |
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