Identification of epidermal growth factor receptor-positive glioblastoma using lipid-encapsulated targeted superparamagnetic iron oxide nanoparticles in vitro

Autor: Wan Zhen Huang, Ping Huei Tsai, Ahmed Atef Ahmed Ali, Chia Feng Lu, Yu-Chieh Jill Kao, Huai Lu Chen, Hua Shan Liu, Fei Ting Hsu, Ray Jade Chen, Cheng Yu Chen, Gilbert Aaron Lee
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Immunoconjugates
Cetuximab
Gene Expression
Pharmaceutical Science
Medicine (miscellaneous)
Ligands
Applied Microbiology and Biotechnology
Antineoplastic Agents
Immunological

Epidermal growth factor receptor
Magnetite Nanoparticles
Gel electrophoresis
biology
Chemistry
Lipids
Magnetic Resonance Imaging
ErbB Receptors
medicine.anatomical_structure
lcsh:R855-855.5
Molecular Medicine
Neuroglia
Antibody
Protein Binding
medicine.drug
lcsh:Medical technology
Drug Compounding
lcsh:Biotechnology
Biomedical Engineering
Bioengineering
03 medical and health sciences
Cell Line
Tumor

lcsh:TP248.13-248.65
Biomarkers
Tumor

medicine
Humans
Magnetic resonance imaging (MRI)
Research
Epidermal growth factor receptor (EGFR)
Molecular biology
Molecular medicine
In vitro
030104 developmental biology
Cell culture
Cancer research
biology.protein
Lipid-encapsulated nanoparticle
Targeted superparamagnetic iron oxide (SPIO) nanoparticle
Glioblastoma
Zdroj: Journal of Nanobiotechnology, Vol 15, Iss 1, Pp 1-13 (2017)
Journal of Nanobiotechnology
ISSN: 1477-3155
Popis: Background Targeted superparamagnetic iron oxide (SPIO) nanoparticles have emerged as a promising biomarker detection tool for molecular magnetic resonance (MR) image diagnosis. To identify patients who could benefit from Epidermal growth factor receptor (EGFR)-targeted therapies, we introduce lipid-encapsulated SPIO nanoparticles and hypothesized that anti-EGFR antibody cetuximab conjugated of such nanoparticles can be used to identify EGFR-positive glioblastomas in non-invasive T2 MR image assays. The newly introduced lipid-coated SPIOs, which imitate biological cell surface and thus inherited innate nonfouling property, were utilized to reduce nonspecific binding to off-targeted cells and prevent agglomeration that commonly occurs in nanoparticles. Results The synthesized targeted EGFR-antibody-conjugated SPIO (EGFR-SPIO) nanoparticles were characterized using dynamic light scattering, zeta potential assays, gel electrophoresis mobility shift assays, transmission electron microscopy (TEM) images, and cell line affinity assays, and the results showed that the conjugation was successful. The targeting efficiency of the synthesized EGFR-SPIO nanoparticles was confirmed through Prussian blue staining and TEM images by using glioblastoma cell lines with high or low EGFR expression levels. The EGFR-SPIO nanoparticles preferentially targeted U-251 cells, which have high EGFR expression, and were internalized by cells in a prolonged incubation condition. Moreover, the T2 MR relaxation time of EGFR-SPIO nanoparticles could be used for successfully identifying glioblastoma cells with elevated EGFR expression in vitro and distinguishing U-251 cells from U-87MG cells, which have low EFGR expression. Conclusion These findings reveal that the lipid-encapsulated EGFR-SPIO nanoparticles can specifically target cells with elevated EGFR expression in the three tested human glioblastoma cell lines. The results of this study can be used for noninvasive molecular MR image diagnosis in the future. Electronic supplementary material The online version of this article (10.1186/s12951-017-0313-2) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE