A self‐reinforced activatable photosensitizer prodrug enabling synergistic photodynamic and chemotherapy
Abstract As a novel drug development paradigm, selective activation of prodrugs provides the potential for precise tumor chemotherapy, thereby presenting an opportunity for advancing cancer treatment. The combination of photodynamic therapy (PDT) and prodrug can enhance the therapeutic efficacy whil...
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Smart Molecules |
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| Online Access: | https://doi.org/10.1002/smo.20240005 |
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| _version_ | 1846114474707124224 |
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| author | Daipeng Huang Jikai Yin Yang Zou Haiqiao Huang Saran Long Wen Sun Jianjun Du Jiangli Fan Xiaojun Peng |
| author_facet | Daipeng Huang Jikai Yin Yang Zou Haiqiao Huang Saran Long Wen Sun Jianjun Du Jiangli Fan Xiaojun Peng |
| author_sort | Daipeng Huang |
| collection | DOAJ |
| description | Abstract As a novel drug development paradigm, selective activation of prodrugs provides the potential for precise tumor chemotherapy, thereby presenting an opportunity for advancing cancer treatment. The combination of photodynamic therapy (PDT) and prodrug can enhance the therapeutic efficacy while simultaneously enabling real‐time monitoring of drug distribution and release. However, the tumor hypoxia microenvironment and the frequent high‐dose administration of prodrugs significantly impede therapeutic efficacy and escalate treatment‐related risks. Herein, a tumor microenvironment‐specific release prodrug is constructed, termed NBS‐2S‐5FU. Under the influence of glutathione (GSH), NBS‐2S‐5FU undergoes activation, leading to the release of photosensitizer NBS and chemotherapeutic agent 5‐FU derivatives. Under irradiation, NBS produces sufficient superoxide radical (O2−•) while 5‐FU derivatives inhibit DNA biosynthesis, thereby effectively suppressing tumor growth at low doses. Subsequent in vivo studies utilizing NBS‐2S‐5FU liposomes exhibit outstanding anti‐cancer effectiveness. This study highlights a promising direction for advancing combined prodrugs that integrate PDT and chemotherapy. |
| format | Article |
| id | doaj-art-cc35ade1bcca4606a9cb2c7fcef6b42f |
| institution | Kabale University |
| issn | 2751-4587 2751-4595 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Smart Molecules |
| spelling | doaj-art-cc35ade1bcca4606a9cb2c7fcef6b42f2024-12-20T12:25:07ZengWileySmart Molecules2751-45872751-45952024-12-0124n/an/a10.1002/smo.20240005A self‐reinforced activatable photosensitizer prodrug enabling synergistic photodynamic and chemotherapyDaipeng Huang0Jikai Yin1Yang Zou2Haiqiao Huang3Saran Long4Wen Sun5Jianjun Du6Jiangli Fan7Xiaojun Peng8State Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical Engineering Dalian University of Technology Dalian ChinaState Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical Engineering Dalian University of Technology Dalian ChinaState Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical Engineering Dalian University of Technology Dalian ChinaState Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical Engineering Dalian University of Technology Dalian ChinaState Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical Engineering Dalian University of Technology Dalian ChinaState Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical Engineering Dalian University of Technology Dalian ChinaState Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical Engineering Dalian University of Technology Dalian ChinaState Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical Engineering Dalian University of Technology Dalian ChinaState Key Laboratory of Fine Chemicals Frontiers Science Center for Smart Materials Oriented Chemical Engineering Dalian University of Technology Dalian ChinaAbstract As a novel drug development paradigm, selective activation of prodrugs provides the potential for precise tumor chemotherapy, thereby presenting an opportunity for advancing cancer treatment. The combination of photodynamic therapy (PDT) and prodrug can enhance the therapeutic efficacy while simultaneously enabling real‐time monitoring of drug distribution and release. However, the tumor hypoxia microenvironment and the frequent high‐dose administration of prodrugs significantly impede therapeutic efficacy and escalate treatment‐related risks. Herein, a tumor microenvironment‐specific release prodrug is constructed, termed NBS‐2S‐5FU. Under the influence of glutathione (GSH), NBS‐2S‐5FU undergoes activation, leading to the release of photosensitizer NBS and chemotherapeutic agent 5‐FU derivatives. Under irradiation, NBS produces sufficient superoxide radical (O2−•) while 5‐FU derivatives inhibit DNA biosynthesis, thereby effectively suppressing tumor growth at low doses. Subsequent in vivo studies utilizing NBS‐2S‐5FU liposomes exhibit outstanding anti‐cancer effectiveness. This study highlights a promising direction for advancing combined prodrugs that integrate PDT and chemotherapy.https://doi.org/10.1002/smo.20240005cell apoptosischemotherapyglutathionephotodynamic therapyprodrug |
| spellingShingle | Daipeng Huang Jikai Yin Yang Zou Haiqiao Huang Saran Long Wen Sun Jianjun Du Jiangli Fan Xiaojun Peng A self‐reinforced activatable photosensitizer prodrug enabling synergistic photodynamic and chemotherapy Smart Molecules cell apoptosis chemotherapy glutathione photodynamic therapy prodrug |
| title | A self‐reinforced activatable photosensitizer prodrug enabling synergistic photodynamic and chemotherapy |
| title_full | A self‐reinforced activatable photosensitizer prodrug enabling synergistic photodynamic and chemotherapy |
| title_fullStr | A self‐reinforced activatable photosensitizer prodrug enabling synergistic photodynamic and chemotherapy |
| title_full_unstemmed | A self‐reinforced activatable photosensitizer prodrug enabling synergistic photodynamic and chemotherapy |
| title_short | A self‐reinforced activatable photosensitizer prodrug enabling synergistic photodynamic and chemotherapy |
| title_sort | self reinforced activatable photosensitizer prodrug enabling synergistic photodynamic and chemotherapy |
| topic | cell apoptosis chemotherapy glutathione photodynamic therapy prodrug |
| url | https://doi.org/10.1002/smo.20240005 |
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