Functionalized Magnetic Nanoparticles for Selective Targeting of Cells
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1241-XX05-03
ABSTRACT Initiation of pathways that lead to proliferation and chemoresistance by Toll-like receptors (TLRs) is an important factor in cancer progression. Here, we show the response of human cancer cells to TLR signaling inevitably linked to tumor biology. The approach is based on tailored multifunctional magnetic nanoparticles equipped with pathogen-derived ligand (CpG) functioning as TLR agonists to investigate the impact of immune activation on human cancer cells. Magnetic nanoparticles (MnO) were covalently coated with a multifunctional polymer, displaying no cytotoxicity, being able to enter cells while carrying foreign DNA (unmethylated CpG) to recognize intracellular TLR 9. Both, the particle and the nucleic acid are tagged with fluorescent markers for simultaneous visualization inside the cell. Apart from optical imaging, the magnetism of the particles also allows magnetic resonance imaging of organisms. INTRODUCTION A key aspect of developing an in vivo approach to cancer diagnosis and treatment is the specific targeting of cancer cells. One of the current strategies uses 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 emerging goals for biomedical applications of nanoparticles is their functionalization to impart precise biological functions. They can be loaded with low molecular drugs or ribonucleic acids (RNA) [4] that are inherently difficult to deliver due to their size and polarity. Nanoparticles are attractive probe candidates because of their (i) size and large surfaceto-volume ratio, (ii) chemically tailorable physical properties directly related to size, composition, and shape, (iii) unusual target binding properties, and (iv) structural robustness. Here we have describe a route to biocompatible materials by functionalization of nanoparticles using multifunctional polymers that simultaneously bind to inorganic nanoparticles, target molecules through specific anchor groups and carry a fluorophor for optical detection. MnO nanopartic
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