Pathogen‐Mimicking MnO Nanoparticles for Selective Activation of the TLR9 Pathway and Imaging of Cancer Cells |
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Authors: | Mohammed Ibrahim Shukoor Filipe Natalio Muhammad Nawaz Tahir Matthias Wiens Marco Tarantola Helen Annal Therese Matthias Barz Stefan Weber Maxim Terekhov Heinz C Schröder Werner E G Müller Andreas Janshoff Patrick Theato Rudolf Zentel Laura Maria Schreiber Wolfgang Tremel |
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Affiliation: | 1. Institute for Inorganic Chemistry Johannes Gutenberg University Duesbergweg 10–14, 55099 Mainz (Germany);2. Institute for Physiological Chemistry Department for Applied Molecular Genetics Johannes Gutenberg University Duesbergweg 6, 55099 Mainz (Germany);3. Institute of Physical Chemistry Georg August University of G?ttingen Tammannstr. 6, 37077 G?ttingen (Germany);4. Institute for Organic Chemistry Johannes Gutenberg University Duesbergweg 10–14, 55099 Mainz (Germany);5. Department of Medical Physics Clinic and Polyclinic for Diagnostic and Interventional Radiology Langenbeckstra?e 1, 55131 Mainz (Germany) |
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Abstract: | Here, design of the first pathogen‐mimicking metal oxide nanoparticles with the ability to enter cancer cells and to selectively target and activate the TLR9 pathway, and with optical and MR imaging capabilities, is reported. The immobilization of ssDNA (CpG ODN 2006) on MnO nanoparticles is performed via the phosphoramidite route using a multifunctional polymer. The multifunctional polymer used for the nanoparticle surface modification not only affords a protective organic biocompatible shell but also provides an efficient and convenient means for loading immunostimulatory oligonucleotides. Since fluorescent molecules are amenable to photodetection, a chromophore (Rhodamine) is introduced into the polymer chain to trace the nanoparticles in Caki‐1 (human kidney cancer) cells. The ssDNA coupled nanoparticles are used to target Toll‐like receptors 9 (TLR9) receptors inside the cells and to activate the classical TLR cascade. The presence of TLR9 is demonstrated independently in the Caki‐1 cell line by western blotting and immunostaining techniques. The magnetic properties of the MnO core make functionalized MnO nanoparticles potential diagnostic agents for magnetic resonance imaging (MRI) thereby enabling multimodal detection by a combination of MR and optical imaging methods. The trimodal nanoparticles allow the imaging of cellular trafficking by different means and simultaneously are an effective drug carrier system. |
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Keywords: | biosensors cell recognition cell surface receptors cell trafficking manganese oxide nanoparticles |
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