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Modular peptide-functionalized gold nanorods for effective Glioblastoma multicellular tumor spheroid targeting


Glioblastoma multiforme (GBM) contains a population of tumor initiating stem-like cells, termed cancer stem cells (CSCs). These CSCs, which are resistant to chemo- and radiotherapy, are thought to persist after treatment and drive tumor recurrence. Thus, it is believed that the elimination of CSCs can lead to GBM remission. GBM CSCs express Nestin on their surface, and can be therefore targeted via this protein. Gold nanorods (AuNRs) functionalized with an engineered, modular peptide that recognizes Nestin (NesPEG-AuNRs), were used to target models of solid tumors originated from human GBM CSC multicellular tumor spheroids (MCTS). In our study, we show that NesPEG-AuNRs have low cytotoxicity, are efficiently taken up by MCTS, and distribute uniformly throughout our tumor models, not only at the periphery as often seen in other nanoparticle systems. NesPEG-AuNR uptake by MCTS appears to be mediated by an energy/caveolae endocytic mechanism. Moreover, plasmon excitation of AuNRs in the near-infrared (NIR) region results in the production of localized heat. Consequently, NesPEG-AuNR cytotoxicity is only observed during NIR-irradiation in MCTS with a high intracellular AuNR content. Intracellular accumulation/diffusion of NesPEG-AuNRs and NIR-irradiation, results in photothermal induced GBM CSC apoptosis and in MCTS growth inhibition. In summary, these data suggest that the combination of the Nestin recognizing peptide with AuNRs, contribute to better tumor accumulation/penetration, and thus in GBM CSC elimination. Moreover, due to the modularity of our peptide design, the Nestin-binding peptide sequence can be exchanged for peptides targeting other surface markers for the treatment of various tumor types.

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Publication details

The article was received on 28 Nov 2017, accepted on 28 Feb 2018 and first published on 28 Feb 2018

Article type: Paper
DOI: 10.1039/C7BM01107E
Citation: Biomater. Sci., 2018, Accepted Manuscript
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    Modular peptide-functionalized gold nanorods for effective Glioblastoma multicellular tumor spheroid targeting

    D. P. Nunes Goncalves, D. M. Park, T. Schmidt and C. Werner, Biomater. Sci., 2018, Accepted Manuscript , DOI: 10.1039/C7BM01107E

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