Functionalized Magnetic Nanoparticles for Selective Targeting of Cells
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1140-HH12-01
Functionalized Magnetic Nanoparticles for Selective Targeting of Cells
Tremel, Wolfgang; Shukoor, Mohammed; Natalio, Filipe; Tahir, Muhammad; Wiens, Matthias; Schladt, Thomas; Barz, Matthias; Theato, Patrick; Schröder, Heinz; Müller, Werner Universität Mainz - Institut für Anorganische Chemie und Analytische Chemie, Mainz, Germany
ABSTRACT MnO nanoparticles were conjugated to single stranded DNA (ssDNA), Cytosinphosphatidyl-Guanosin oligonucleotide (CpG ODN) to detect and activate Toll-like (TLR9) receptors in cells and to follow nanoparticle cellular trafficking by different means of imaging while at the same time serving as a drug carrier system. By virtue of their magnetic properties these nanoparticles may serve as vehicles for the transport of target molecules into cells, while the fluorescent target ligand allows optical detection simultaneously. INTRODUCTION One of the difficult aspects of developing an in vivo approach to cancer treatment is the specific targeting of cancer cells. One strategy is the use of therapeutic nucleotides. Microbial pathogens that penetrate epithelial barriers and invade tissues are usually encountered by three types of sentinel immune cells: tissue macrophages, mast cells and immature dendritic cells. These sentinels must be able to distinguish between fragments of apoptotic cells generated during normal tissue turnover and particles that are indicative of microbial assaults and infections. The molecules responsible for making this pivotal distinction belong to the family of pattern recognition receptors (PRRs), of which Toll-like receptors (TLRs) are best characterized [1]. TLRs recognize highly conserved microbial structures that were termed pathogen-associated molecular patterns (PAMPs). Stimulation of macrophages or mast cells through their TLRs leads to the synthesis and secretion of proinflammatory cytokines and lipid mediators, thereby initiating an inflammatory response that recruits both soluble immune components and immune cells from the blood [2]. On the other hand, TLR stimulation of dendritic cells induces the initiation of an adaptive immune response [3]. One of the exciting new research subjects involving magnetic nanoparticles is their application in biological systems, including targeted drug delivery, magnetic resonance imaging (MRI), biosensors and magnetic hyperthermia therapy. Nanoparticles are attractive probe candidates because of their (i) small size (1-50 nm) and correspondingly large surface-to-volume ratio, (ii) chemically tailorable physical properties which directly relate to size, composition, and shape, (iii) unusual target binding properties, and (iv) overall structural robustness. The size of a nanomaterial can be an advantage over a bulk structure, because a target binding event involving the nanomaterial can have a significant effect on its physical and chemical properties, thereby providing a mode of signal transduction not necessarily available with a bulk structure made of the same material. We have designed a pathogen-mimicking
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