Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor‐Specific and Ferroptosis‐Augmented Sonodynamic Therapy
Abstract Covalent organic frameworks (COFs) have attracted increasing attention for biomedical applications. COFs‐based nanosensitizers with uniform nanoscale morphology and tumor‐specific curative effects are in high demand; however, their synthesis is yet challenging. In this study, distinct COF n...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202206009 |
| _version_ | 1797895062556770304 |
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| author | Shanshan Zhang Shujun Xia Liang Chen Yu Chen Jianqiao Zhou |
| author_facet | Shanshan Zhang Shujun Xia Liang Chen Yu Chen Jianqiao Zhou |
| author_sort | Shanshan Zhang |
| collection | DOAJ |
| description | Abstract Covalent organic frameworks (COFs) have attracted increasing attention for biomedical applications. COFs‐based nanosensitizers with uniform nanoscale morphology and tumor‐specific curative effects are in high demand; however, their synthesis is yet challenging. In this study, distinct COF nanobowls are synthesized in a controlled manner and engineered as activatable nanosensitizers with tumor‐specific sonodynamic activity. High crystallinity ensures an ordered porous structure of COF nanobowls for the efficient loading of the small‐molecule sonosensitizer rose bengal (RB). To circumvent non‐specific damage to normal tissues, the sonosensitization effect is specifically inhibited by the in situ growth of manganese oxide (MnOx) on RB‐loaded COFs. Upon reaction with tumor‐overexpressed glutathione (GSH), the “gatekeeper” MnOx is rapidly decomposed to recover the reactive oxygen species (ROS) generation capability of the COF nanosensitizers under ultrasound irradiation. Increased intracellular ROS stress and GSH consumption concomitantly induce ferroptosis to improve sonodynamic efficacy. Additionally, the unconventional bowl‐shaped morphology renders the nanosensitizers with enhanced tumor accumulation and retention. The combination of tumor‐specific sonodynamic therapy and ferroptosis achieves high efficacy in killing cancer cells and inhibiting tumor growth. This study paves the way for the development of COF nanosensitizers with unconventional morphologies for biomedicine, offering a paradigm to realize activatable and ferroptosis‐augmented sonodynamic tumor therapy. |
| first_indexed | 2024-04-10T07:20:25Z |
| format | Article |
| id | doaj.art-28ad33a4f75a42d69f3ee797e67087bb |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-10T07:20:25Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-28ad33a4f75a42d69f3ee797e67087bb2023-02-24T12:27:40ZengWileyAdvanced Science2198-38442023-02-01106n/an/a10.1002/advs.202206009Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor‐Specific and Ferroptosis‐Augmented Sonodynamic TherapyShanshan Zhang0Shujun Xia1Liang Chen2Yu Chen3Jianqiao Zhou4Department of Ultrasound Ruijin Hospital Shanghai Jiaotong University School of Medicine Shanghai 200025 P. R. ChinaDepartment of Ultrasound Ruijin Hospital Shanghai Jiaotong University School of Medicine Shanghai 200025 P. R. ChinaMaterdicine Lab School of Life Sciences Shanghai University Shanghai 200444 P. R. ChinaMaterdicine Lab School of Life Sciences Shanghai University Shanghai 200444 P. R. ChinaDepartment of Ultrasound Ruijin Hospital Shanghai Jiaotong University School of Medicine Shanghai 200025 P. R. ChinaAbstract Covalent organic frameworks (COFs) have attracted increasing attention for biomedical applications. COFs‐based nanosensitizers with uniform nanoscale morphology and tumor‐specific curative effects are in high demand; however, their synthesis is yet challenging. In this study, distinct COF nanobowls are synthesized in a controlled manner and engineered as activatable nanosensitizers with tumor‐specific sonodynamic activity. High crystallinity ensures an ordered porous structure of COF nanobowls for the efficient loading of the small‐molecule sonosensitizer rose bengal (RB). To circumvent non‐specific damage to normal tissues, the sonosensitization effect is specifically inhibited by the in situ growth of manganese oxide (MnOx) on RB‐loaded COFs. Upon reaction with tumor‐overexpressed glutathione (GSH), the “gatekeeper” MnOx is rapidly decomposed to recover the reactive oxygen species (ROS) generation capability of the COF nanosensitizers under ultrasound irradiation. Increased intracellular ROS stress and GSH consumption concomitantly induce ferroptosis to improve sonodynamic efficacy. Additionally, the unconventional bowl‐shaped morphology renders the nanosensitizers with enhanced tumor accumulation and retention. The combination of tumor‐specific sonodynamic therapy and ferroptosis achieves high efficacy in killing cancer cells and inhibiting tumor growth. This study paves the way for the development of COF nanosensitizers with unconventional morphologies for biomedicine, offering a paradigm to realize activatable and ferroptosis‐augmented sonodynamic tumor therapy.https://doi.org/10.1002/advs.202206009activatable therapybiomedicinecovalent organic frameworksferroptosissonodynamic therapy |
| spellingShingle | Shanshan Zhang Shujun Xia Liang Chen Yu Chen Jianqiao Zhou Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor‐Specific and Ferroptosis‐Augmented Sonodynamic Therapy Advanced Science activatable therapy biomedicine covalent organic frameworks ferroptosis sonodynamic therapy |
| title | Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor‐Specific and Ferroptosis‐Augmented Sonodynamic Therapy |
| title_full | Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor‐Specific and Ferroptosis‐Augmented Sonodynamic Therapy |
| title_fullStr | Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor‐Specific and Ferroptosis‐Augmented Sonodynamic Therapy |
| title_full_unstemmed | Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor‐Specific and Ferroptosis‐Augmented Sonodynamic Therapy |
| title_short | Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor‐Specific and Ferroptosis‐Augmented Sonodynamic Therapy |
| title_sort | covalent organic framework nanobowls as activatable nanosensitizers for tumor specific and ferroptosis augmented sonodynamic therapy |
| topic | activatable therapy biomedicine covalent organic frameworks ferroptosis sonodynamic therapy |
| url | https://doi.org/10.1002/advs.202206009 |
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