Site-specific nanomodulator capable of modulation apoptosis for enhanced colorectal cancer chemo-photothermal therapy
Abstract Background Colorectal cancer (CRC) is a common malignancy with the second highest mortality and the third highest morbidity worldwide. However, the overall survival of patients is unsatisfactory, thus requiring more effective clinical strategies. Celastrol (CLT), a natural bioactive compoun...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-023-01779-5 |
| _version_ | 1797945771917574144 |
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| author | Shuqi Wang Li Zhou Hailong Tian Bowen Li Miao Su Qiong Li Edouard C. Nice Canhua Huang Jichun Shao Tao He |
| author_facet | Shuqi Wang Li Zhou Hailong Tian Bowen Li Miao Su Qiong Li Edouard C. Nice Canhua Huang Jichun Shao Tao He |
| author_sort | Shuqi Wang |
| collection | DOAJ |
| description | Abstract Background Colorectal cancer (CRC) is a common malignancy with the second highest mortality and the third highest morbidity worldwide. However, the overall survival of patients is unsatisfactory, thus requiring more effective clinical strategies. Celastrol (CLT), a natural bioactive compound, has been reported to induce reactive oxygen species (ROS)-mediated apoptosis to exhibit significant antitumor effects against CRC. However, the poor water solubility, low targeting ability, and bioavailability of CLT have limited its application, and CLT-induced protective autophagy weakens its therapeutic efficiency. Results We designed a targeted chemo-phototherapy nanoplatform (HCR NPs) to improve the application of CLT. The codelivery of IR820 and CLT in HCR NPs solved the water-soluble problem of CLT and enhanced apoptosis via IR820-mediated hyperthermia. In addition, hydroxychloroquine (HCQ) conjugated to hyaluronic acid (HA) not only increased the active targeting of HCR NPs but also inhibited CLT-induced protective autophagy to exacerbate apoptosis, thus achieving an amplified antitumor effect. Importantly, the HCR NPs exhibited an excellent therapeutic effect on CRC both in vitro and in vivo. Conclusion The HCR NPs presented in this study may not merely provide a new reference for the clinical application of CLT but also result in an attractive strategy for CRC treatment. |
| first_indexed | 2024-04-10T21:00:25Z |
| format | Article |
| id | doaj.art-d92835118d3e4206b41a2574a29ee11f |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-10T21:00:25Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-d92835118d3e4206b41a2574a29ee11f2023-01-22T12:24:00ZengBMCJournal of Nanobiotechnology1477-31552023-01-0121111510.1186/s12951-023-01779-5Site-specific nanomodulator capable of modulation apoptosis for enhanced colorectal cancer chemo-photothermal therapyShuqi Wang0Li Zhou1Hailong Tian2Bowen Li3Miao Su4Qiong Li5Edouard C. Nice6Canhua Huang7Jichun Shao8Tao He9Institute for Cancer Medicine, School of Basic Medical Sciences, Southwest Medical UniversityKey Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical UniversityState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China, School of Basic Medical Sciences and Forensic Medicine, Collaborative Innovation Center for Biotherapy, Sichuan UniversityState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China, School of Basic Medical Sciences and Forensic Medicine, Collaborative Innovation Center for Biotherapy, Sichuan UniversityState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China, School of Basic Medical Sciences and Forensic Medicine, Collaborative Innovation Center for Biotherapy, Sichuan UniversityState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China, School of Basic Medical Sciences and Forensic Medicine, Collaborative Innovation Center for Biotherapy, Sichuan UniversityDepartment of Biochemistry and Molecular Biology, Monash UniversityState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China, School of Basic Medical Sciences and Forensic Medicine, Collaborative Innovation Center for Biotherapy, Sichuan UniversityThe Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 HospitalInstitute for Cancer Medicine, School of Basic Medical Sciences, Southwest Medical UniversityAbstract Background Colorectal cancer (CRC) is a common malignancy with the second highest mortality and the third highest morbidity worldwide. However, the overall survival of patients is unsatisfactory, thus requiring more effective clinical strategies. Celastrol (CLT), a natural bioactive compound, has been reported to induce reactive oxygen species (ROS)-mediated apoptosis to exhibit significant antitumor effects against CRC. However, the poor water solubility, low targeting ability, and bioavailability of CLT have limited its application, and CLT-induced protective autophagy weakens its therapeutic efficiency. Results We designed a targeted chemo-phototherapy nanoplatform (HCR NPs) to improve the application of CLT. The codelivery of IR820 and CLT in HCR NPs solved the water-soluble problem of CLT and enhanced apoptosis via IR820-mediated hyperthermia. In addition, hydroxychloroquine (HCQ) conjugated to hyaluronic acid (HA) not only increased the active targeting of HCR NPs but also inhibited CLT-induced protective autophagy to exacerbate apoptosis, thus achieving an amplified antitumor effect. Importantly, the HCR NPs exhibited an excellent therapeutic effect on CRC both in vitro and in vivo. Conclusion The HCR NPs presented in this study may not merely provide a new reference for the clinical application of CLT but also result in an attractive strategy for CRC treatment.https://doi.org/10.1186/s12951-023-01779-5Colorectal cancerCelastrolIR820ChemotherapyPhotothermal therapy |
| spellingShingle | Shuqi Wang Li Zhou Hailong Tian Bowen Li Miao Su Qiong Li Edouard C. Nice Canhua Huang Jichun Shao Tao He Site-specific nanomodulator capable of modulation apoptosis for enhanced colorectal cancer chemo-photothermal therapy Journal of Nanobiotechnology Colorectal cancer Celastrol IR820 Chemotherapy Photothermal therapy |
| title | Site-specific nanomodulator capable of modulation apoptosis for enhanced colorectal cancer chemo-photothermal therapy |
| title_full | Site-specific nanomodulator capable of modulation apoptosis for enhanced colorectal cancer chemo-photothermal therapy |
| title_fullStr | Site-specific nanomodulator capable of modulation apoptosis for enhanced colorectal cancer chemo-photothermal therapy |
| title_full_unstemmed | Site-specific nanomodulator capable of modulation apoptosis for enhanced colorectal cancer chemo-photothermal therapy |
| title_short | Site-specific nanomodulator capable of modulation apoptosis for enhanced colorectal cancer chemo-photothermal therapy |
| title_sort | site specific nanomodulator capable of modulation apoptosis for enhanced colorectal cancer chemo photothermal therapy |
| topic | Colorectal cancer Celastrol IR820 Chemotherapy Photothermal therapy |
| url | https://doi.org/10.1186/s12951-023-01779-5 |
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