Abstract

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.

Original languageEnglish
Article number86
JournalJournal of Nanobiotechnology
Volume15
Issue number1
DOIs
Publication statusPublished - Nov 22 2017

Fingerprint

Glioblastoma
Iron oxides
Epidermal Growth Factor Receptor
Nanoparticles
Lipids
Magnetic resonance
Assays
Magnetic Resonance Spectroscopy
Cells
Transmission Electron Microscopy
Antibodies
Cell Line
ferric oxide
In Vitro Techniques
Epidermal Growth Factor
Transmission electron microscopy
Electrophoretic Mobility Shift Assay
Biomarkers
Dynamic light scattering
Zeta potential

Keywords

  • Epidermal growth factor receptor (EGFR)
  • Glioblastoma
  • Lipid-encapsulated nanoparticle
  • Magnetic resonance imaging (MRI)
  • Targeted superparamagnetic iron oxide (SPIO) nanoparticle

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Applied Microbiology and Biotechnology
  • Pharmaceutical Science

Cite this

Identification of epidermal growth factor receptor-positive glioblastoma using lipid-encapsulated targeted superparamagnetic iron oxide nanoparticles in vitro. / Chen, Huai Lu; Hsu, Fei Ting; Kao, Yu Chieh Jill; Liu, Hua Shan; Huang, Wan Zhen; Lu, Chia Feng; Tsai, Ping Huei; Ali, Ahmed Atef Ahmed; Lee, Gilbert Aaron; Chen, Ray Jade; Chen, Cheng Yu.

In: Journal of Nanobiotechnology, Vol. 15, No. 1, 86, 22.11.2017.

Research output: Contribution to journalArticle

@article{fd0232d9971c48a9a8b78c2cd6c9ef88,
title = "Identification of epidermal growth factor receptor-positive glioblastoma using lipid-encapsulated targeted superparamagnetic iron oxide nanoparticles in vitro",
abstract = "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.",
keywords = "Epidermal growth factor receptor (EGFR), Glioblastoma, Lipid-encapsulated nanoparticle, Magnetic resonance imaging (MRI), Targeted superparamagnetic iron oxide (SPIO) nanoparticle",
author = "Chen, {Huai Lu} and Hsu, {Fei Ting} and Kao, {Yu Chieh Jill} and Liu, {Hua Shan} and Huang, {Wan Zhen} and Lu, {Chia Feng} and Tsai, {Ping Huei} and Ali, {Ahmed Atef Ahmed} and Lee, {Gilbert Aaron} and Chen, {Ray Jade} and Chen, {Cheng Yu}",
year = "2017",
month = "11",
day = "22",
doi = "10.1186/s12951-017-0313-2",
language = "English",
volume = "15",
journal = "Journal of Nanobiotechnology",
issn = "1477-3155",
publisher = "BioMed Central",
number = "1",

}

TY - JOUR

T1 - Identification of epidermal growth factor receptor-positive glioblastoma using lipid-encapsulated targeted superparamagnetic iron oxide nanoparticles in vitro

AU - Chen, Huai Lu

AU - Hsu, Fei Ting

AU - Kao, Yu Chieh Jill

AU - Liu, Hua Shan

AU - Huang, Wan Zhen

AU - Lu, Chia Feng

AU - Tsai, Ping Huei

AU - Ali, Ahmed Atef Ahmed

AU - Lee, Gilbert Aaron

AU - Chen, Ray Jade

AU - Chen, Cheng Yu

PY - 2017/11/22

Y1 - 2017/11/22

N2 - 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.

AB - 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.

KW - Epidermal growth factor receptor (EGFR)

KW - Glioblastoma

KW - Lipid-encapsulated nanoparticle

KW - Magnetic resonance imaging (MRI)

KW - Targeted superparamagnetic iron oxide (SPIO) nanoparticle

UR - http://www.scopus.com/inward/record.url?scp=85034768900&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85034768900&partnerID=8YFLogxK

U2 - 10.1186/s12951-017-0313-2

DO - 10.1186/s12951-017-0313-2

M3 - Article

C2 - 29166921

AN - SCOPUS:85034768900

VL - 15

JO - Journal of Nanobiotechnology

JF - Journal of Nanobiotechnology

SN - 1477-3155

IS - 1

M1 - 86

ER -