Tuning Nanoparticle Uptake: Live-Cell Imaging Reveals Two Distinct Endocytosis Mechanisms Mediated by Natural and Artificial EGFR Targeting Ligand

Therapeutic nanoparticles can be directed to cancer cells by incorporating selective targeting ligands. Here, we investigate the epidermal growth factor receptor (EGFR)-mediated endocytosis of gene carriers (polyplexes) either targeted with natural EGF or GE11, a short synthetic EGFR-binding peptide...

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Veröffentlicht in:Nano letters 2012-07, Vol.12 (7), p.3417-3423
Hauptverfasser: Mickler, Frauke M, Möckl, Leonhard, Ruthardt, Nadia, Ogris, Manfred, Wagner, Ernst, Bräuchle, Christoph
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container_end_page 3423
container_issue 7
container_start_page 3417
container_title Nano letters
container_volume 12
creator Mickler, Frauke M
Möckl, Leonhard
Ruthardt, Nadia
Ogris, Manfred
Wagner, Ernst
Bräuchle, Christoph
description Therapeutic nanoparticles can be directed to cancer cells by incorporating selective targeting ligands. Here, we investigate the epidermal growth factor receptor (EGFR)-mediated endocytosis of gene carriers (polyplexes) either targeted with natural EGF or GE11, a short synthetic EGFR-binding peptide. Highly sensitive live-cell fluorescence microcopy with single particle resolution unraveled the existence of two different uptake mechanisms; EGF triggers accelerated nanoparticle endocytosis due to its dual active role in receptor binding and signaling activation. For GE11, an alternative EGFR signaling independent, actin-driven pathway is presented.
doi_str_mv 10.1021/nl300395q
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subjects Actins - metabolism
Binding
Cell Line, Tumor
Cross-disciplinary physics: materials science
rheology
Drug Carriers - chemistry
Drug Carriers - metabolism
Endocytosis
Exact sciences and technology
Gene Transfer Techniques
Genes
Growth factors
Humans
Ligands
Materials science
Microscopy, Fluorescence
Nanocrystalline materials
Nanoparticles
Nanoparticles - chemistry
Nanoscale materials and structures: fabrication and characterization
Nanostructure
Peptides - chemistry
Peptides - metabolism
Physics
Receptor, Epidermal Growth Factor - chemistry
Receptor, Epidermal Growth Factor - metabolism
Receptors
Signal Transduction
Tuning
Uptakes
title Tuning Nanoparticle Uptake: Live-Cell Imaging Reveals Two Distinct Endocytosis Mechanisms Mediated by Natural and Artificial EGFR Targeting Ligand
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