7th Annual Symposium
Physics of Cancer
Leipzig, Germany
October 4-6, 2016
Invited Talk
Death by Gold: Targeting Invasive Glioblastoma Cells by Peptide-Functionalized Gold Nanorods
Diana P.N. Goncalves1, Raul D. Rodriguez2, Thomas Kurth3, Laura J. Bray1,4, Marcus Binner1, Christiane Jungnickel5, Fatih N. Gür6, Steve W. Poser7, Thorsten Schmidt6, Dietrich R. T. Zahn2, Andreas Androutsellis-Theotokis7, Michael Schlierf5, Carsten Werner1
1Leibniz Institute of Polymer Research Dresden, Max Bergmann Center of Biomaterials Dresden, Hohe Str. 6, 01069 Dresden, Germany
2Institute of Physics, Technische Universität Chemnitz, 09107 Chemnitz, Germany
3Electron Microscopy Facility, DFG - Center of Regenerative Therapies Dresden, Technische Universität Dresden, Fetscherstr. 105, 01307 Dresden, Germany
4Institute of Health and Biomedical Innovation, Queensland University, 60 Musk Avenue, Kelvin Grove, QLD 4059, Australia
5B CUBE - Center of Macromolecular Bioenineering, Technische Universität Dresden, 01307 Dresden, Germany
6Cluster of Excellence Center of Advancing Electronics Dresden (cfaed), Technische Universität Dresden, 01062 Dresden, Germany
7University Clinic Carl-Gustav Carus, Technische Universität Dresden, 01062 Dresden, Germany
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Cancer stem cells (CSCs) are known to be responsible for drug resistance and tumor recurrence in several cancer types, making their eradication a primary objective in cancer therapy. Glioblastoma multiforme (GBM) tumors are usually composed of a highly infiltrating CSC subpopulation, which has Nestin as a putative marker. Since the majority of these infiltrating cells are able to elude conventional therapies, we have developed a gold nanorod- (AuNR) peptide-biosensor capable of specific recognition and selective eradication of Nestin-positive GBM (GBM-Nes+) infiltrating cells, by photohermolysis. The AuNR-peptide biosensor was evaluated regarding heating abilities, cell selectivity, cell uptake pathway, and photohthermal activity in mono- and co-culture systems containing Nes+ and Nestin-negative (Nes-) GBM cells. Biodegradable three dimensional (3D) hydrogels, composed of star shaped poly(ethyleneglycol) (starPEG) covalently connected to matrix metalloproteinase-susceptible peptides and heparin (starPEG-MMP-heparin), were used to recreate GBM tumor microenvironments, and for the assessment of AuNR photothermal activity. Finally, the obtained 3D culture results were then compared with two dimentional monolayer cultures.
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