Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy
Abstract Background Hypoxia is a characteristic of solid tumors that can lead to tumor angiogenesis and early metastasis, and addressing hypoxia presents tremendous challenges. In this work, a nanomedicine based on oxygen-absorbing perfluorotributylamine (PFA) and the bioreductive prodrug tirapazami...
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BMC
2021-09-01
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Series: | Journal of Nanobiotechnology |
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Online Access: | https://doi.org/10.1186/s12951-021-01013-0 |
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author | Hongfang Chen You Fu Kai Feng Yifan Zhou Xin Wang Haohan Huang Yan Chen Wenhao Wang Yuanjing Xu Haijun Tian Yuanqing Mao Jinwu Wang Zhiyuan Zhang |
author_facet | Hongfang Chen You Fu Kai Feng Yifan Zhou Xin Wang Haohan Huang Yan Chen Wenhao Wang Yuanjing Xu Haijun Tian Yuanqing Mao Jinwu Wang Zhiyuan Zhang |
author_sort | Hongfang Chen |
collection | DOAJ |
description | Abstract Background Hypoxia is a characteristic of solid tumors that can lead to tumor angiogenesis and early metastasis, and addressing hypoxia presents tremendous challenges. In this work, a nanomedicine based on oxygen-absorbing perfluorotributylamine (PFA) and the bioreductive prodrug tirapazamine (TPZ) was prepared by using a polydopamine (PDA)-coated UiO-66 metal organic framework (MOF) as the drug carrier. Results The results showed that TPZ/PFA@UiO-66@PDA nanoparticles significantly enhanced hypoxia, induced cell apoptosis in vitro through the oxygen-dependent HIF-1α pathway and decreased oxygen levels in vivo after intratumoral injection. In addition, our study demonstrated that TPZ/PFA@UiO-66@PDA nanoparticles can accumulate in the tumor region after tail vein injection and effectively inhibit tumor growth when combined with photothermal therapy (PTT). TPZ/PFA@UiO-66@PDA nanoparticles increased HIF-1α expression while did not promote the expression of CD31 in vivo during the experiment. Conclusions By using TPZ and PFA and the enhanced permeability and retention effect of nanoparticles, TPZ/PFA@UiO-66@PDA can target tumor tissues, enhance hypoxia in the tumor microenvironment, and activate TPZ. Combined with PTT, the growth of osteosarcoma xenografts can be effectively inhibited. Graphic abstract |
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institution | Directory Open Access Journal |
issn | 1477-3155 |
language | English |
last_indexed | 2024-04-14T02:34:56Z |
publishDate | 2021-09-01 |
publisher | BMC |
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series | Journal of Nanobiotechnology |
spelling | doaj.art-d936f8174ef8450ea2566bef510772e32022-12-22T02:17:33ZengBMCJournal of Nanobiotechnology1477-31552021-09-0119111810.1186/s12951-021-01013-0Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapyHongfang Chen0You Fu1Kai Feng2Yifan Zhou3Xin Wang4Haohan Huang5Yan Chen6Wenhao Wang7Yuanjing Xu8Haijun Tian9Yuanqing Mao10Jinwu Wang11Zhiyuan Zhang12Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral & Maxillofacial - Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of StomatologyInstitute of Microsurgery on Extremities, Department of Orthopedic Surgery, Shanghai Jiaotong University Affiliated Sixth People’s HospitalShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineCollege of Medicine, Southwest Jiaotong UniversitySchool of Biomedical Engineering, Shanghai Jiao Tong UniversityShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral & Maxillofacial - Head & Neck Oncology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of StomatologyAbstract Background Hypoxia is a characteristic of solid tumors that can lead to tumor angiogenesis and early metastasis, and addressing hypoxia presents tremendous challenges. In this work, a nanomedicine based on oxygen-absorbing perfluorotributylamine (PFA) and the bioreductive prodrug tirapazamine (TPZ) was prepared by using a polydopamine (PDA)-coated UiO-66 metal organic framework (MOF) as the drug carrier. Results The results showed that TPZ/PFA@UiO-66@PDA nanoparticles significantly enhanced hypoxia, induced cell apoptosis in vitro through the oxygen-dependent HIF-1α pathway and decreased oxygen levels in vivo after intratumoral injection. In addition, our study demonstrated that TPZ/PFA@UiO-66@PDA nanoparticles can accumulate in the tumor region after tail vein injection and effectively inhibit tumor growth when combined with photothermal therapy (PTT). TPZ/PFA@UiO-66@PDA nanoparticles increased HIF-1α expression while did not promote the expression of CD31 in vivo during the experiment. Conclusions By using TPZ and PFA and the enhanced permeability and retention effect of nanoparticles, TPZ/PFA@UiO-66@PDA can target tumor tissues, enhance hypoxia in the tumor microenvironment, and activate TPZ. Combined with PTT, the growth of osteosarcoma xenografts can be effectively inhibited. Graphic abstracthttps://doi.org/10.1186/s12951-021-01013-0Metal-organic framework (MOF)Tumor hypoxiaPhotothermal therapy (PTT)Osteosarcoma |
spellingShingle | Hongfang Chen You Fu Kai Feng Yifan Zhou Xin Wang Haohan Huang Yan Chen Wenhao Wang Yuanjing Xu Haijun Tian Yuanqing Mao Jinwu Wang Zhiyuan Zhang Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy Journal of Nanobiotechnology Metal-organic framework (MOF) Tumor hypoxia Photothermal therapy (PTT) Osteosarcoma |
title | Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy |
title_full | Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy |
title_fullStr | Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy |
title_full_unstemmed | Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy |
title_short | Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy |
title_sort | polydopamine coated uio 66 nanoparticles loaded with perfluorotributylamine tirapazamine for hypoxia activated osteosarcoma therapy |
topic | Metal-organic framework (MOF) Tumor hypoxia Photothermal therapy (PTT) Osteosarcoma |
url | https://doi.org/10.1186/s12951-021-01013-0 |
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