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Nano Lett. 2012 Jul 11;12(7):3417-23. doi: 10.1021/nl300395q. Epub 2012 Jun 5.

Tuning nanoparticle uptake: live-cell imaging reveals two distinct endocytosis mechanisms mediated by natural and artificial EGFR targeting ligand.

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Department of Chemistry and Center for NanoScience (CeNS), Ludwig-Maximilians-Universität München, Butenandtstrasse 5-13, D-81377 München, Germany.


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.

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