Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms
Abstract Background No prominent advancements in osteosarcoma (OS) treatment have been made in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, the lack of targeted photosensitizers for OS treatment severely limits its applications. Results In this...
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-021-01201-y |
| _version_ | 1798035447164698624 |
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| author | Yang Wang Liang Zhang Guosheng Zhao Yuan Zhang Fangbiao Zhan Zhiyu Chen Tao He Yang Cao Lan Hao Zhigang Wang Zhengxue Quan Yunsheng Ou |
| author_facet | Yang Wang Liang Zhang Guosheng Zhao Yuan Zhang Fangbiao Zhan Zhiyu Chen Tao He Yang Cao Lan Hao Zhigang Wang Zhengxue Quan Yunsheng Ou |
| author_sort | Yang Wang |
| collection | DOAJ |
| description | Abstract Background No prominent advancements in osteosarcoma (OS) treatment have been made in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, the lack of targeted photosensitizers for OS treatment severely limits its applications. Results In this study, we constructed a potential theranostic nanoplatform by using (poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IR780 into the shell (PLGA-IR780 NPs), which were further camouflaged with human OS cell membranes from the HOS cell line (MH-PLGA-IR780 NPs). These constructed NPs showed the capacity for homologous targeting with excellent photoacoustic (PA)/fluorescence (FL) imaging ability. Benefitting from their homologous targeting capacity, MH-PLGA-IR780 NPs obviously promoted cell endocytosis in vitro and tumor accumulation in vivo, which could further improve PDT performance under near-infrared (NIR) irradiation. In addition, to their homologous targeting and PA/FL dual-mode imaging ability, MH-PLGA-IR780 NPs had advantages in penetrating deeper into tumor tissues and in real-time dynamic distribution monitoring in vivo, which laid a foundation for further clinical applications in OS. Moreover, we demonstrated that PDT guided by the constructed NPs could significantly induce HOS cells apoptosis and ferroptosis via excessive accumulation of reactive oxygen species (ROS), and further determined that the potential anticancer molecular mechanism of apoptosis was triggered by the release of cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and that ferroptosis caused the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and the inactivation of glutathione peroxidase 4 (GPX4), synergistically leading to excessive accumulation of Lipid-ROS and Lipid peroxides (LPOs). Concurrently, MH-PLGA-IR780 NPs-guided PDT also showed an obvious inhibitory effect on tumor growth in vivo. Conclusion These results suggest that this homologous targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and contributes a new and promising approach for OS therapy. Graphical Abstract |
| first_indexed | 2024-04-11T20:58:26Z |
| format | Article |
| id | doaj.art-7d7f1dfde0d44aaf86e3bc650886d730 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-11T20:58:26Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
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| series | Journal of Nanobiotechnology |
| spelling | doaj.art-7d7f1dfde0d44aaf86e3bc650886d7302022-12-22T04:03:37ZengBMCJournal of Nanobiotechnology1477-31552022-02-0120112810.1186/s12951-021-01201-yHomologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanismsYang Wang0Liang Zhang1Guosheng Zhao2Yuan Zhang3Fangbiao Zhan4Zhiyu Chen5Tao He6Yang Cao7Lan Hao8Zhigang Wang9Zhengxue Quan10Yunsheng Ou11Department of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Ultrasound, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopedic Surgery, Children’s Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, China International Science and Technology Cooperation Base of Child Development and Critical DisordersDepartment of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Orthopedic Surgery, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Background No prominent advancements in osteosarcoma (OS) treatment have been made in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, the lack of targeted photosensitizers for OS treatment severely limits its applications. Results In this study, we constructed a potential theranostic nanoplatform by using (poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) encapsulating IR780 into the shell (PLGA-IR780 NPs), which were further camouflaged with human OS cell membranes from the HOS cell line (MH-PLGA-IR780 NPs). These constructed NPs showed the capacity for homologous targeting with excellent photoacoustic (PA)/fluorescence (FL) imaging ability. Benefitting from their homologous targeting capacity, MH-PLGA-IR780 NPs obviously promoted cell endocytosis in vitro and tumor accumulation in vivo, which could further improve PDT performance under near-infrared (NIR) irradiation. In addition, to their homologous targeting and PA/FL dual-mode imaging ability, MH-PLGA-IR780 NPs had advantages in penetrating deeper into tumor tissues and in real-time dynamic distribution monitoring in vivo, which laid a foundation for further clinical applications in OS. Moreover, we demonstrated that PDT guided by the constructed NPs could significantly induce HOS cells apoptosis and ferroptosis via excessive accumulation of reactive oxygen species (ROS), and further determined that the potential anticancer molecular mechanism of apoptosis was triggered by the release of cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and that ferroptosis caused the activation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy and the inactivation of glutathione peroxidase 4 (GPX4), synergistically leading to excessive accumulation of Lipid-ROS and Lipid peroxides (LPOs). Concurrently, MH-PLGA-IR780 NPs-guided PDT also showed an obvious inhibitory effect on tumor growth in vivo. Conclusion These results suggest that this homologous targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and contributes a new and promising approach for OS therapy. Graphical Abstracthttps://doi.org/10.1186/s12951-021-01201-yPDTOSHomologous targetingApoptosisFerroptosis |
| spellingShingle | Yang Wang Liang Zhang Guosheng Zhao Yuan Zhang Fangbiao Zhan Zhiyu Chen Tao He Yang Cao Lan Hao Zhigang Wang Zhengxue Quan Yunsheng Ou Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms Journal of Nanobiotechnology PDT OS Homologous targeting Apoptosis Ferroptosis |
| title | Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms |
| title_full | Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms |
| title_fullStr | Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms |
| title_full_unstemmed | Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms |
| title_short | Homologous targeting nanoparticles for enhanced PDT against osteosarcoma HOS cells and the related molecular mechanisms |
| title_sort | homologous targeting nanoparticles for enhanced pdt against osteosarcoma hos cells and the related molecular mechanisms |
| topic | PDT OS Homologous targeting Apoptosis Ferroptosis |
| url | https://doi.org/10.1186/s12951-021-01201-y |
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