Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization
Abstract Nasopharyngeal carcinoma (NPC), a malignancy highly prevalent in East and Southeast Asia, is primarily treated with radiotherapy (RT). However, hypoxia-induced radioresistance presents a significant challenge. Nanozymes, nanomaterials with catalase-like activity, have emerged as a promising...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56134-z |
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| author | Ruofei Zhang Yanfang Shen Xiaoying Zhou Jianru Li Hanqing Zhao Zixia Zhang Jun Zhao Hongjun Jin Shuanshuan Guo Hui Ding Guohui Nie Zhe Zhang Ying Wang Xiyun Yan Kelong Fan |
| author_facet | Ruofei Zhang Yanfang Shen Xiaoying Zhou Jianru Li Hanqing Zhao Zixia Zhang Jun Zhao Hongjun Jin Shuanshuan Guo Hui Ding Guohui Nie Zhe Zhang Ying Wang Xiyun Yan Kelong Fan |
| author_sort | Ruofei Zhang |
| collection | DOAJ |
| description | Abstract Nasopharyngeal carcinoma (NPC), a malignancy highly prevalent in East and Southeast Asia, is primarily treated with radiotherapy (RT). However, hypoxia-induced radioresistance presents a significant challenge. Nanozymes, nanomaterials with catalase-like activity, have emerged as a promising strategy for radiosensitization by converting elevated hydrogen peroxide in the tumor microenvironment into oxygen. Despite their potential, effectively targeting hypoxic lesions has been difficult. Here, we identify transferrin receptor 1 (TfR1) as an upregulated target in NPC, with its expression levels positively correlated with hypoxia. Human heavy-chain ferritin, a specific ligand of TfR1, selectively recognizes hypoxic NPC lesions in preclinical models. Based on these findings, we design a hypoxia-targeted nanozyme by loading platinum nanoparticles into ferritin. This nanozyme exhibits enhanced catalase-like activity and effectively alleviates tumor hypoxia in NPC xenografts. When combined with RT, a single injection of the nanozyme significantly inhibits tumor growth and prolongs mouse survival, outperforming sodium glycididazole, a clinically used radiosensitizer. In summary, our findings highlight TfR1 as an accessible cell surface target in hypoxic NPC lesions. The nanozyme targeting TfR1 holds promise for enhancing the therapeutic effectiveness of RT in NPC through an in situ oxygen-generation mechanism. |
| format | Article |
| id | doaj-art-922f7462e08d45c7b93a24c5b506ba3f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-922f7462e08d45c7b93a24c5b506ba3f2025-01-26T12:42:00ZengNature PortfolioNature Communications2041-17232025-01-0116112010.1038/s41467-025-56134-zHypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitizationRuofei Zhang0Yanfang Shen1Xiaoying Zhou2Jianru Li3Hanqing Zhao4Zixia Zhang5Jun Zhao6Hongjun Jin7Shuanshuan Guo8Hui Ding9Guohui Nie10Zhe Zhang11Ying Wang12Xiyun Yan13Kelong Fan14CAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules (CAS), CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesDepartment of Nuclear Medicine, The Fifth Affiliated Hospital, Sun Yat-sen UniversityKey Laboratory of High-Incidence-Tumor Prevention & Treatment, Guangxi Medical University, Ministry of EducationCAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules (CAS), CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesCAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules (CAS), CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesCAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules (CAS), CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesKey Laboratory of High-Incidence-Tumor Prevention & Treatment, Guangxi Medical University, Ministry of EducationGuangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital, Sun Yat-sen UniversityCancer Center, The Fifth Affiliated Hospital of Sun Yat-Sen UniversityShenzhen Key Laboratory of nanozymes and Translational Cancer Research, Shenzhen Second People’s Hospital/the First Affiliated Hospital of Shenzhen University Health Science CenterShenzhen Key Laboratory of nanozymes and Translational Cancer Research, Shenzhen Second People’s Hospital/the First Affiliated Hospital of Shenzhen University Health Science CenterDepartment of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical UniversityDepartment of Nuclear Medicine, The Fifth Affiliated Hospital, Sun Yat-sen UniversityCAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules (CAS), CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesCAS Engineering Laboratory for Nanozyme, Key Laboratory of Biomacromolecules (CAS), CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesAbstract Nasopharyngeal carcinoma (NPC), a malignancy highly prevalent in East and Southeast Asia, is primarily treated with radiotherapy (RT). However, hypoxia-induced radioresistance presents a significant challenge. Nanozymes, nanomaterials with catalase-like activity, have emerged as a promising strategy for radiosensitization by converting elevated hydrogen peroxide in the tumor microenvironment into oxygen. Despite their potential, effectively targeting hypoxic lesions has been difficult. Here, we identify transferrin receptor 1 (TfR1) as an upregulated target in NPC, with its expression levels positively correlated with hypoxia. Human heavy-chain ferritin, a specific ligand of TfR1, selectively recognizes hypoxic NPC lesions in preclinical models. Based on these findings, we design a hypoxia-targeted nanozyme by loading platinum nanoparticles into ferritin. This nanozyme exhibits enhanced catalase-like activity and effectively alleviates tumor hypoxia in NPC xenografts. When combined with RT, a single injection of the nanozyme significantly inhibits tumor growth and prolongs mouse survival, outperforming sodium glycididazole, a clinically used radiosensitizer. In summary, our findings highlight TfR1 as an accessible cell surface target in hypoxic NPC lesions. The nanozyme targeting TfR1 holds promise for enhancing the therapeutic effectiveness of RT in NPC through an in situ oxygen-generation mechanism.https://doi.org/10.1038/s41467-025-56134-z |
| spellingShingle | Ruofei Zhang Yanfang Shen Xiaoying Zhou Jianru Li Hanqing Zhao Zixia Zhang Jun Zhao Hongjun Jin Shuanshuan Guo Hui Ding Guohui Nie Zhe Zhang Ying Wang Xiyun Yan Kelong Fan Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization Nature Communications |
| title | Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization |
| title_full | Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization |
| title_fullStr | Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization |
| title_full_unstemmed | Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization |
| title_short | Hypoxia-tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization |
| title_sort | hypoxia tropic delivery of nanozymes targeting transferrin receptor 1 for nasopharyngeal carcinoma radiotherapy sensitization |
| url | https://doi.org/10.1038/s41467-025-56134-z |
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