Photodynamic-therapy and chemotherapy of TPBC-PEG nanoplatform encapsulated triptolide synergistically inhibit primary osteosarcoma growth and pulmonary metastasis by activating HIPPO signaling
Osteosarcoma is the most common bone malignancy in children and adolescents with a less than 30% overall survival rate for those with metastatic disease, particularly pulmonary metastases. Drug resistance hinders the effectiveness of current chemotherapies, making osteosarcoma a leading cause of mor...
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Elsevier
2024-12-01
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| Series: | Materials & Design |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0264127524008578 |
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| author | Junli Chang Wenyi Wang Fulai Zhao Xingyuan Sun Suxia Guo Chujie Zhou Peng Zhao Junjie Tong Weian Zhang Yanping Yang |
| author_facet | Junli Chang Wenyi Wang Fulai Zhao Xingyuan Sun Suxia Guo Chujie Zhou Peng Zhao Junjie Tong Weian Zhang Yanping Yang |
| author_sort | Junli Chang |
| collection | DOAJ |
| description | Osteosarcoma is the most common bone malignancy in children and adolescents with a less than 30% overall survival rate for those with metastatic disease, particularly pulmonary metastases. Drug resistance hinders the effectiveness of current chemotherapies, making osteosarcoma a leading cause of mortality and an urgent requirement of new therapeutics in this population. Here, we developed a triptolide (TP)-loaded, pH-responsive and near-infrared light-activated nanoplatform (TP-TPBC-PEG) with photodynamic therapy (PDT) to target osteosarcoma cells both in vitro and in vivo. Our results demonstrated that PDT and chemotherapy of TP-TPBC-PEG synergistically reduced cell viability, colony proliferation, migration, and invasion in vitro, and inhibited osteosarcoma growth and pulmonary metastasis in vivo which the nano-micelles were intravenously injected to intratibia injection induced osteosarcoma mouse models, showing enhanced osteosarcoma cell killing by nanoparticle inflating in response to acidic endosomal pH and sensitized osteosarcoma cells to TP chemotherapy. Importantly, the nano-micelles did not exhibit organ toxicity in vivo. Dual-luciferase reporter gene and nuclear/ cytoplasm protein expression assays identified the involvement of HIPPO signaling pathway in mediating these effects. Overall, our study provides a promising therapeutic approach for treating primary osteosarcoma and preventing pulmonary metastases by activating the HIPPO signaling pathway. |
| format | Article |
| id | doaj-art-751fabb290d24c64b0875e6a772c197c |
| institution | Kabale University |
| issn | 0264-1275 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials & Design |
| spelling | doaj-art-751fabb290d24c64b0875e6a772c197c2024-12-21T04:27:34ZengElsevierMaterials & Design0264-12752024-12-01248113482Photodynamic-therapy and chemotherapy of TPBC-PEG nanoplatform encapsulated triptolide synergistically inhibit primary osteosarcoma growth and pulmonary metastasis by activating HIPPO signalingJunli Chang0Wenyi Wang1Fulai Zhao2Xingyuan Sun3Suxia Guo4Chujie Zhou5Peng Zhao6Junjie Tong7Weian Zhang8Yanping Yang9Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, PR ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, PR ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, PR ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, PR ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, PR ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, PR ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, PR ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, PR ChinaShanghai Key Laboratory of Advanced Polymeric Materials, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China; Corresponding authors at: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China (Y. Yang); Shanghai Key Laboratory of Advanced Polymeric Materials, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China (W. Zhang).Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China; Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai 200032, PR China; Corresponding authors at: Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, PR China (Y. Yang); Shanghai Key Laboratory of Advanced Polymeric Materials, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China (W. Zhang).Osteosarcoma is the most common bone malignancy in children and adolescents with a less than 30% overall survival rate for those with metastatic disease, particularly pulmonary metastases. Drug resistance hinders the effectiveness of current chemotherapies, making osteosarcoma a leading cause of mortality and an urgent requirement of new therapeutics in this population. Here, we developed a triptolide (TP)-loaded, pH-responsive and near-infrared light-activated nanoplatform (TP-TPBC-PEG) with photodynamic therapy (PDT) to target osteosarcoma cells both in vitro and in vivo. Our results demonstrated that PDT and chemotherapy of TP-TPBC-PEG synergistically reduced cell viability, colony proliferation, migration, and invasion in vitro, and inhibited osteosarcoma growth and pulmonary metastasis in vivo which the nano-micelles were intravenously injected to intratibia injection induced osteosarcoma mouse models, showing enhanced osteosarcoma cell killing by nanoparticle inflating in response to acidic endosomal pH and sensitized osteosarcoma cells to TP chemotherapy. Importantly, the nano-micelles did not exhibit organ toxicity in vivo. Dual-luciferase reporter gene and nuclear/ cytoplasm protein expression assays identified the involvement of HIPPO signaling pathway in mediating these effects. Overall, our study provides a promising therapeutic approach for treating primary osteosarcoma and preventing pulmonary metastases by activating the HIPPO signaling pathway.http://www.sciencedirect.com/science/article/pii/S0264127524008578OsteosarcomaPulmonary metastasesTriptolidePhotodynamic therapyTP-TPBC-PEGHIPPO signaling |
| spellingShingle | Junli Chang Wenyi Wang Fulai Zhao Xingyuan Sun Suxia Guo Chujie Zhou Peng Zhao Junjie Tong Weian Zhang Yanping Yang Photodynamic-therapy and chemotherapy of TPBC-PEG nanoplatform encapsulated triptolide synergistically inhibit primary osteosarcoma growth and pulmonary metastasis by activating HIPPO signaling Materials & Design Osteosarcoma Pulmonary metastases Triptolide Photodynamic therapy TP-TPBC-PEG HIPPO signaling |
| title | Photodynamic-therapy and chemotherapy of TPBC-PEG nanoplatform encapsulated triptolide synergistically inhibit primary osteosarcoma growth and pulmonary metastasis by activating HIPPO signaling |
| title_full | Photodynamic-therapy and chemotherapy of TPBC-PEG nanoplatform encapsulated triptolide synergistically inhibit primary osteosarcoma growth and pulmonary metastasis by activating HIPPO signaling |
| title_fullStr | Photodynamic-therapy and chemotherapy of TPBC-PEG nanoplatform encapsulated triptolide synergistically inhibit primary osteosarcoma growth and pulmonary metastasis by activating HIPPO signaling |
| title_full_unstemmed | Photodynamic-therapy and chemotherapy of TPBC-PEG nanoplatform encapsulated triptolide synergistically inhibit primary osteosarcoma growth and pulmonary metastasis by activating HIPPO signaling |
| title_short | Photodynamic-therapy and chemotherapy of TPBC-PEG nanoplatform encapsulated triptolide synergistically inhibit primary osteosarcoma growth and pulmonary metastasis by activating HIPPO signaling |
| title_sort | photodynamic therapy and chemotherapy of tpbc peg nanoplatform encapsulated triptolide synergistically inhibit primary osteosarcoma growth and pulmonary metastasis by activating hippo signaling |
| topic | Osteosarcoma Pulmonary metastases Triptolide Photodynamic therapy TP-TPBC-PEG HIPPO signaling |
| url | http://www.sciencedirect.com/science/article/pii/S0264127524008578 |
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