Probing real-time response to multitargeted tyrosine kinase inhibitor 4-n-(3'-Bromo-Phenyl) amino-6, 7-dimethoxyquinazoline in single living cells using biofuntionalized quantum dots

May Show Chen, Chia Yeh Liu, Wei Ting Wang, Chien Ting Hsu, Chih Ming Cheng, Jing Shin Tsai, Keng Liang Ou, Tzu Sen Yang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Recently, the quinazolinederivative, 4-N-(3'-bromo-phenyl) amino-6, 7-dimethoxyquinazoline (PD153035), has been reported not only to inhibit the epidermal growth factor receptor (EGFR) tyrosine kinase but also to bind to DNA double helical structures by intercalation. However, several important pharmacology issues such as whether PD153035 is a specific and reversible inhibitor of the EGFR tyrosine kinase should be addressed in more detail. In this study, we propose a nanotechnology-based approach to monitoring the real-time EGF-EGFR complex trafficking process and its relationship to cytoskeleton, as well as spatio-temporal cellular response to PD153035 at the single-cell level. We utilize the biofunctionalized quntum dots (QDs) conjugated with EGF to monitor the cellular distribution of QD-EGF-EGFR complexes, which can provide a more direct access to probing the spatio-temporal distribution of EGF-EGFR complex in the absence and presence of PD153035. We found that QD-EGF-EGFR complexes undergo retrograde transport before receptor-mediated internalization. In addition, QD-EGF-EGFR complexes colocalize with actin filaments, especially in filopodia regions. Furthermore, the cellular distribution of fluorescing QDs was strongly localized inside the cell after washing PD153035 for time period longer than 15 minutes. This observation demonstrated that PD153035 could be removed from the intracellular kinase domain, namely, PD153035 is a reversible EGFR inhibitor. We anticipate these approaches based on the platform at single-cell level could be applied to build a quick screening method for detection and treatment evaluation of many types of cancer expressed high levels of EGFR.

Original languageEnglish
JournalJournal of Nanomedicine and Nanotechnology
Volume2
Issue number6
DOIs
Publication statusPublished - Nov 2011

Fingerprint

Quantum Dots
Epidermal Growth Factor Receptor
Protein-Tyrosine Kinases
Semiconductor quantum dots
Cells
Epidermal Growth Factor
Nanotechnology
Pseudopodia
Intercalation
4-((3-bromophenyl)amino)-6,7-dimethoxyquinazoline
Cytoskeleton
Actin Cytoskeleton
Washing
Actins
Screening
Phosphotransferases
Pharmacology
Monitoring

Keywords

  • Biofuntionalized quantum dots
  • Epidermal growth factor receptor
  • Non-small cell lung cancer
  • PD153035
  • Single living cell
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Bioengineering
  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Pharmaceutical Science

Cite this

Probing real-time response to multitargeted tyrosine kinase inhibitor 4-n-(3'-Bromo-Phenyl) amino-6, 7-dimethoxyquinazoline in single living cells using biofuntionalized quantum dots. / Chen, May Show; Liu, Chia Yeh; Wang, Wei Ting; Hsu, Chien Ting; Cheng, Chih Ming; Tsai, Jing Shin; Ou, Keng Liang; Yang, Tzu Sen.

In: Journal of Nanomedicine and Nanotechnology, Vol. 2, No. 6, 11.2011.

Research output: Contribution to journalArticle

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abstract = "Recently, the quinazolinederivative, 4-N-(3'-bromo-phenyl) amino-6, 7-dimethoxyquinazoline (PD153035), has been reported not only to inhibit the epidermal growth factor receptor (EGFR) tyrosine kinase but also to bind to DNA double helical structures by intercalation. However, several important pharmacology issues such as whether PD153035 is a specific and reversible inhibitor of the EGFR tyrosine kinase should be addressed in more detail. In this study, we propose a nanotechnology-based approach to monitoring the real-time EGF-EGFR complex trafficking process and its relationship to cytoskeleton, as well as spatio-temporal cellular response to PD153035 at the single-cell level. We utilize the biofunctionalized quntum dots (QDs) conjugated with EGF to monitor the cellular distribution of QD-EGF-EGFR complexes, which can provide a more direct access to probing the spatio-temporal distribution of EGF-EGFR complex in the absence and presence of PD153035. We found that QD-EGF-EGFR complexes undergo retrograde transport before receptor-mediated internalization. In addition, QD-EGF-EGFR complexes colocalize with actin filaments, especially in filopodia regions. Furthermore, the cellular distribution of fluorescing QDs was strongly localized inside the cell after washing PD153035 for time period longer than 15 minutes. This observation demonstrated that PD153035 could be removed from the intracellular kinase domain, namely, PD153035 is a reversible EGFR inhibitor. We anticipate these approaches based on the platform at single-cell level could be applied to build a quick screening method for detection and treatment evaluation of many types of cancer expressed high levels of EGFR.",
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AU - Chen, May Show

AU - Liu, Chia Yeh

AU - Wang, Wei Ting

AU - Hsu, Chien Ting

AU - Cheng, Chih Ming

AU - Tsai, Jing Shin

AU - Ou, Keng Liang

AU - Yang, Tzu Sen

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AB - Recently, the quinazolinederivative, 4-N-(3'-bromo-phenyl) amino-6, 7-dimethoxyquinazoline (PD153035), has been reported not only to inhibit the epidermal growth factor receptor (EGFR) tyrosine kinase but also to bind to DNA double helical structures by intercalation. However, several important pharmacology issues such as whether PD153035 is a specific and reversible inhibitor of the EGFR tyrosine kinase should be addressed in more detail. In this study, we propose a nanotechnology-based approach to monitoring the real-time EGF-EGFR complex trafficking process and its relationship to cytoskeleton, as well as spatio-temporal cellular response to PD153035 at the single-cell level. We utilize the biofunctionalized quntum dots (QDs) conjugated with EGF to monitor the cellular distribution of QD-EGF-EGFR complexes, which can provide a more direct access to probing the spatio-temporal distribution of EGF-EGFR complex in the absence and presence of PD153035. We found that QD-EGF-EGFR complexes undergo retrograde transport before receptor-mediated internalization. In addition, QD-EGF-EGFR complexes colocalize with actin filaments, especially in filopodia regions. Furthermore, the cellular distribution of fluorescing QDs was strongly localized inside the cell after washing PD153035 for time period longer than 15 minutes. This observation demonstrated that PD153035 could be removed from the intracellular kinase domain, namely, PD153035 is a reversible EGFR inhibitor. We anticipate these approaches based on the platform at single-cell level could be applied to build a quick screening method for detection and treatment evaluation of many types of cancer expressed high levels of EGFR.

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