Enzyme-sequential responsive core-satellite nanomedicine enables activatable near-infrared-II photoacoustic imaging-guided chemotherapy cascade-enhanced radiotherapy
Abstract The standard treatment for various types of cancers typically involves the combination of concurrent localized radiotherapy and systemic chemotherapy. However, no treatment options have been reported that utilize chemotherapy cascade-enhanced radiotherapy. In this study, we report a core-sa...
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BMC
2025-06-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-025-03531-7 |
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| author | Wenjing Xiao Xiao Yang Mengzhen Wang Zeyu Jiang Heyi Zhang Mengqing Gong Lin Zhao Jibin Song Qinrui Fu |
| author_facet | Wenjing Xiao Xiao Yang Mengzhen Wang Zeyu Jiang Heyi Zhang Mengqing Gong Lin Zhao Jibin Song Qinrui Fu |
| author_sort | Wenjing Xiao |
| collection | DOAJ |
| description | Abstract The standard treatment for various types of cancers typically involves the combination of concurrent localized radiotherapy and systemic chemotherapy. However, no treatment options have been reported that utilize chemotherapy cascade-enhanced radiotherapy. In this study, we report a core-satellite nanomedicine designed to enhance radiotherapeutic effects through a cascade mechanism by triggering the release of a potent chemotherapeutic agent in response to trypsin. We synthesized a functional enzyme-sequential responsive nanomedicine, DOX@Gel-DEVD-AuNR, which consists of gelatin nanoparticles loaded with the chemotherapeutic drug doxorubicin (DOX). These nanoparticles are covalently linked to gold nanorods (AuNR) via a caspase-3 specific DEVD peptide substrate. Upon trypsin activation, the DOX@Gel-DEVD-AuNR formulation releases DOX, thereby enhancing chemotherapy efficacy against tumors. Simultaneously, it activates caspase-3, inducing the aggregation of AuNRs, which in turn activates a near-infrared-II photoacoustic signal. This signal is crucial for determining the optimal timing for X-ray irradiation. The resulting large-size AuNRs aggregates promote their accumulation within tumors by preventing the migration and backflow of AuNRs, thereby improving radiotherapeutic effects. Consequently, when combined with image-guided X-ray irradiation, DOX@Gel-DEVD-AuNR induces significant cytotoxicity in cancer cells and effectively inhibits tumor growth. Our study underscores the potential application of enzyme catalysis-mediated chemistry in activating nanomedicine for activatable image-guided chemotherapy cascade-enhanced radiotherapy. |
| format | Article |
| id | doaj-art-e4184f69a88247b8a244c54de6b71352 |
| institution | DOAJ |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-e4184f69a88247b8a244c54de6b713522025-08-20T02:39:47ZengBMCJournal of Nanobiotechnology1477-31552025-06-0123111310.1186/s12951-025-03531-7Enzyme-sequential responsive core-satellite nanomedicine enables activatable near-infrared-II photoacoustic imaging-guided chemotherapy cascade-enhanced radiotherapyWenjing Xiao0Xiao Yang1Mengzhen Wang2Zeyu Jiang3Heyi Zhang4Mengqing Gong5Lin Zhao6Jibin Song7Qinrui Fu8Department of Radiotherapy, The Affiliated Hospital of Qingdao University, Qingdao UniversityInstitute of Chronic Disease, College of Medicine, Qingdao UniversityInstitute of Chronic Disease, College of Medicine, Qingdao UniversityInstitute of Chronic Disease, College of Medicine, Qingdao UniversityInstitute of Chronic Disease, College of Medicine, Qingdao UniversityInstitute of Chronic Disease, College of Medicine, Qingdao UniversityDepartment of Radiotherapy, The Affiliated Hospital of Qingdao University, Qingdao UniversityState Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical TechnologyInstitute of Chronic Disease, College of Medicine, Qingdao UniversityAbstract The standard treatment for various types of cancers typically involves the combination of concurrent localized radiotherapy and systemic chemotherapy. However, no treatment options have been reported that utilize chemotherapy cascade-enhanced radiotherapy. In this study, we report a core-satellite nanomedicine designed to enhance radiotherapeutic effects through a cascade mechanism by triggering the release of a potent chemotherapeutic agent in response to trypsin. We synthesized a functional enzyme-sequential responsive nanomedicine, DOX@Gel-DEVD-AuNR, which consists of gelatin nanoparticles loaded with the chemotherapeutic drug doxorubicin (DOX). These nanoparticles are covalently linked to gold nanorods (AuNR) via a caspase-3 specific DEVD peptide substrate. Upon trypsin activation, the DOX@Gel-DEVD-AuNR formulation releases DOX, thereby enhancing chemotherapy efficacy against tumors. Simultaneously, it activates caspase-3, inducing the aggregation of AuNRs, which in turn activates a near-infrared-II photoacoustic signal. This signal is crucial for determining the optimal timing for X-ray irradiation. The resulting large-size AuNRs aggregates promote their accumulation within tumors by preventing the migration and backflow of AuNRs, thereby improving radiotherapeutic effects. Consequently, when combined with image-guided X-ray irradiation, DOX@Gel-DEVD-AuNR induces significant cytotoxicity in cancer cells and effectively inhibits tumor growth. Our study underscores the potential application of enzyme catalysis-mediated chemistry in activating nanomedicine for activatable image-guided chemotherapy cascade-enhanced radiotherapy.https://doi.org/10.1186/s12951-025-03531-7Activatable NIR-II photoacoustic imagingEnzyme-sequential responsive nanomedicineChemotherapyRadiotherapyCascade therapy |
| spellingShingle | Wenjing Xiao Xiao Yang Mengzhen Wang Zeyu Jiang Heyi Zhang Mengqing Gong Lin Zhao Jibin Song Qinrui Fu Enzyme-sequential responsive core-satellite nanomedicine enables activatable near-infrared-II photoacoustic imaging-guided chemotherapy cascade-enhanced radiotherapy Journal of Nanobiotechnology Activatable NIR-II photoacoustic imaging Enzyme-sequential responsive nanomedicine Chemotherapy Radiotherapy Cascade therapy |
| title | Enzyme-sequential responsive core-satellite nanomedicine enables activatable near-infrared-II photoacoustic imaging-guided chemotherapy cascade-enhanced radiotherapy |
| title_full | Enzyme-sequential responsive core-satellite nanomedicine enables activatable near-infrared-II photoacoustic imaging-guided chemotherapy cascade-enhanced radiotherapy |
| title_fullStr | Enzyme-sequential responsive core-satellite nanomedicine enables activatable near-infrared-II photoacoustic imaging-guided chemotherapy cascade-enhanced radiotherapy |
| title_full_unstemmed | Enzyme-sequential responsive core-satellite nanomedicine enables activatable near-infrared-II photoacoustic imaging-guided chemotherapy cascade-enhanced radiotherapy |
| title_short | Enzyme-sequential responsive core-satellite nanomedicine enables activatable near-infrared-II photoacoustic imaging-guided chemotherapy cascade-enhanced radiotherapy |
| title_sort | enzyme sequential responsive core satellite nanomedicine enables activatable near infrared ii photoacoustic imaging guided chemotherapy cascade enhanced radiotherapy |
| topic | Activatable NIR-II photoacoustic imaging Enzyme-sequential responsive nanomedicine Chemotherapy Radiotherapy Cascade therapy |
| url | https://doi.org/10.1186/s12951-025-03531-7 |
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