Detection of PD-L1 Expression in Temozolomide-Resistant Glioblastoma by Using PD-L1 Antibodies Conjugated with Lipid‑Coated Superparamagnetic Iron Oxide

Gilbert-Aaron Lee, Wan-Li Lin, Duen Pang Kuo, Yi-Tien Li, Yu Wei Chang, Yung Chieh Chen, Shiu-Wen Huang, Justin Bo Kai Hsu, Cheng-Yu Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: 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.
Original languageEnglish
Pages (from-to)5233-5246
JournalInternational Journal of Nanomedicine
Volume2021
Issue number16
Publication statusPublished - Jul 2021

Keywords

  • PD-L1
  • superparamagnetic iron oxide
  • SPIO
  • magnetic resonance imaging
  • MRI
  • lipid-coated nanoparticle
  • glioblastoma

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