Detection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide
Gilbert Aaron Lee,1,2 Wan-Li Lin,1 Duen-Pang Kuo,3 Yi-Tien Li,4,5 Yu-Wei Chang,1 Yung-Chieh Chen,4,6 Shiu-Wen Huang,1,7,8 Justin Bo-Kai Hsu,1 Cheng-Yu Chen3,4,6,9 1Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan; 2Department of Microbiology and Immunology, School o...
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Dove Medical Press
2021
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oai:doaj.org-article:24d4f10babb1462c8034b568b761dba32021-12-02T18:48:09ZDetection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide1178-2013https://doaj.org/article/24d4f10babb1462c8034b568b761dba32021-07-01T00:00:00Zhttps://www.dovepress.com/detection-of-pd-l1-expression-in-temozolomide-resistant-glioblastoma-b-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Gilbert Aaron Lee,1,2 Wan-Li Lin,1 Duen-Pang Kuo,3 Yi-Tien Li,4,5 Yu-Wei Chang,1 Yung-Chieh Chen,4,6 Shiu-Wen Huang,1,7,8 Justin Bo-Kai Hsu,1 Cheng-Yu Chen3,4,6,9 1Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan; 2Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan; 4Translational Imaging Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 5Neuroscience Research Center, Taipei Medical University, Taipei, Taiwan; 6Research Center of Translational Imaging, College of Medicine, Taipei Medical University, Taipei, Taiwan; 7Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; 9Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanCorrespondence: Cheng-Yu ChenDepartment of Radiology, School of Medicine, College of Medicine, Taipei Medical University, No. 251 Wu Hsing Street, Taipei City 110, Taipei, TaiwanEmail sandy0932@gmail.comPurpose: Targeted superparamagnetic iron oxide (SPIO) nanoparticles are a promising tool for molecular magnetic resonance imaging (MRI) diagnosis. Lipid-coated SPIO nanoparticles have a nonfouling property that can reduce nonspecific binding to off-target cells and prevent agglomeration, making them suitable contrast agents for molecular MRI diagnosis. PD-L1 is a poor prognostic factor for patients with glioblastoma. Most recurrent glioblastomas are temozolomide resistant. Diagnostic probes targeting PD-L1 could facilitate early diagnosis and be used to predict responses to targeted PD-L1 immunotherapy in patients with primary or recurrent glioblastoma. We conjugated lipid-coated SPIO nanoparticles with PD-L1 antibodies to identify PD-L1 expression in glioblastoma or temozolomide-resistant glioblastoma by using MRI.Methods: The synthesized PD-L1 antibody-conjugated SPIO (PDL1-SPIO) nanoparticles were characterized using dynamic light scattering, zeta potential assays, transmission electron microscopy images, Prussian blue assay, in vitro cell affinity assay, and animal MRI analysis.Results: PDL1-SPIO exhibited a specific binding capacity to PD-L1 of the mouse glioblastoma cell line (GL261). The presence and quantity of PDL1-SPIO in temozolomide-resistant glioblastoma cells and tumor tissue were confirmed through Prussian blue staining and in vivo T2* map MRI, respectively.Conclusion: This is the first study to demonstrate that PDL1-SPIO can specifically target temozolomide-resistant glioblastoma with PD-L1 expression in the brain and can be quantified through MRI analysis, thus making it suitable for the diagnosis of PD-L1 expression in temozolomide-resistant glioblastoma in vivo.Keywords: PD-L1, superparamagnetic iron oxide, SPIO, magnetic resonance imaging, MRI, lipid-coated nanoparticle, glioblastomaLee GALin WLKuo DPLi YTChang YWChen YCHuang SWHsu JBKChen CYDove Medical Pressarticlepd-l1superparamagnetic iron oxidespiomagnetic resonance imagingmrilipid-coated nanoparticleglioblastomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 5233-5246 (2021) |
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DOAJ |
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EN |
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pd-l1 superparamagnetic iron oxide spio magnetic resonance imaging mri lipid-coated nanoparticle glioblastoma Medicine (General) R5-920 |
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pd-l1 superparamagnetic iron oxide spio magnetic resonance imaging mri lipid-coated nanoparticle glioblastoma Medicine (General) R5-920 Lee GA Lin WL Kuo DP Li YT Chang YW Chen YC Huang SW Hsu JBK Chen CY Detection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide |
| description |
Gilbert Aaron Lee,1,2 Wan-Li Lin,1 Duen-Pang Kuo,3 Yi-Tien Li,4,5 Yu-Wei Chang,1 Yung-Chieh Chen,4,6 Shiu-Wen Huang,1,7,8 Justin Bo-Kai Hsu,1 Cheng-Yu Chen3,4,6,9 1Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan; 2Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 3Department of Medical Imaging, Taipei Medical University Hospital, Taipei, Taiwan; 4Translational Imaging Research Center, Taipei Medical University Hospital, Taipei, Taiwan; 5Neuroscience Research Center, Taipei Medical University, Taipei, Taiwan; 6Research Center of Translational Imaging, College of Medicine, Taipei Medical University, Taipei, Taiwan; 7Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; 9Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanCorrespondence: Cheng-Yu ChenDepartment of Radiology, School of Medicine, College of Medicine, Taipei Medical University, No. 251 Wu Hsing Street, Taipei City 110, Taipei, TaiwanEmail sandy0932@gmail.comPurpose: Targeted superparamagnetic iron oxide (SPIO) nanoparticles are a promising tool for molecular magnetic resonance imaging (MRI) diagnosis. Lipid-coated SPIO nanoparticles have a nonfouling property that can reduce nonspecific binding to off-target cells and prevent agglomeration, making them suitable contrast agents for molecular MRI diagnosis. PD-L1 is a poor prognostic factor for patients with glioblastoma. Most recurrent glioblastomas are temozolomide resistant. Diagnostic probes targeting PD-L1 could facilitate early diagnosis and be used to predict responses to targeted PD-L1 immunotherapy in patients with primary or recurrent glioblastoma. We conjugated lipid-coated SPIO nanoparticles with PD-L1 antibodies to identify PD-L1 expression in glioblastoma or temozolomide-resistant glioblastoma by using MRI.Methods: The synthesized PD-L1 antibody-conjugated SPIO (PDL1-SPIO) nanoparticles were characterized using dynamic light scattering, zeta potential assays, transmission electron microscopy images, Prussian blue assay, in vitro cell affinity assay, and animal MRI analysis.Results: PDL1-SPIO exhibited a specific binding capacity to PD-L1 of the mouse glioblastoma cell line (GL261). The presence and quantity of PDL1-SPIO in temozolomide-resistant glioblastoma cells and tumor tissue were confirmed through Prussian blue staining and in vivo T2* map MRI, respectively.Conclusion: This is the first study to demonstrate that PDL1-SPIO can specifically target temozolomide-resistant glioblastoma with PD-L1 expression in the brain and can be quantified through MRI analysis, thus making it suitable for the diagnosis of PD-L1 expression in temozolomide-resistant glioblastoma in vivo.Keywords: PD-L1, superparamagnetic iron oxide, SPIO, magnetic resonance imaging, MRI, lipid-coated nanoparticle, glioblastoma |
| format |
article |
| author |
Lee GA Lin WL Kuo DP Li YT Chang YW Chen YC Huang SW Hsu JBK Chen CY |
| author_facet |
Lee GA Lin WL Kuo DP Li YT Chang YW Chen YC Huang SW Hsu JBK Chen CY |
| author_sort |
Lee GA |
| title |
Detection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide |
| title_short |
Detection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide |
| title_full |
Detection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide |
| title_fullStr |
Detection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide |
| title_full_unstemmed |
Detection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide |
| title_sort |
detection of pd-l1 expression in temozolomide-resistant glioblastoma by using pd-l1 antibodies conjugated with lipid‑coated superparamagnetic iron oxide |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/24d4f10babb1462c8034b568b761dba3 |
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