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Issue 13, 2015
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Directional Plk1 inhibition-driven cell cycle interruption using amphiphilic thin-coated peptide-lanthanide upconversion nanomaterials as in vivo tumor suppressors

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Abstract

Polo-like kinase 1 (Plk1) is a major serine/threonine protein kinase which regulates key mitotic events such as centrosome duplication, spindle assembly and chromosome separation. Overexpression and aberrant activities of Plk1 can be detected in different types of cancer. Given that the unique polo box domain (PBD) pocket provides an excellent drug target for Plk1 binding and inhibition, we have rationally designed multifunctional lanthanide-doped upconversion nanomaterials. NaGdF4:Yb3+, Er3+ (NaGdF4) and BaGdF5:Yb3+, Er3+ (BaGdF5) nanoparticles of two different sizes (60 nm and 10 nm, respectively) have been thin-coated with Plk1 specific peptides (–P1 = PLHSpT, –P2 = PLHSD, and –P3 = GGPLHSpT) to prepare novel nanomaterials. Comparative studies on cellular uptake, anti-cancer activity and imaging properties were then carried out. The experimental data obtained support our original hypothesis that the designed nanomaterials can successfully deliver Plk1 specific peptides into cancer cells causing Plk1 inhibition while simultaneously allowing direct NIR imaging and monitoring. Among the NaGdF4–Pn and BaGdF5–Pn nanoparticle series prepared in this study, NaGdF4–P1 emerged as the best candidate for Plk1 binding and imaging. NaGdF4–P1 can effectively exert cell cycle G2/M arrest and thus selective tumor inhibition both in vitro and in vivo and as such it offers a potentially interesting system for the development of new cancer therapies.

Graphical abstract: Directional Plk1 inhibition-driven cell cycle interruption using amphiphilic thin-coated peptide-lanthanide upconversion nanomaterials as in vivo tumor suppressors

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Publication details

The article was received on 20 Dec 2014, accepted on 30 Jan 2015 and first published on 05 Feb 2015


Article type: Paper
DOI: 10.1039/C4TB02104E
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J. Mater. Chem. B, 2015,3, 2624-2634
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    Directional Plk1 inhibition-driven cell cycle interruption using amphiphilic thin-coated peptide-lanthanide upconversion nanomaterials as in vivo tumor suppressors

    C. Chan, R. Lan, M. Tsang, D. Zhou, S. Lear, W. Chan, S. L. Cobb, W. Wong, J. Hao, W. Wong and K. Wong, J. Mater. Chem. B, 2015, 3, 2624
    DOI: 10.1039/C4TB02104E

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