Enabling diagnostic technologies that merge the use of nanoscale components and miniaturized detector systems could have a great impact in point-of -care diagnostics. In particular, diagnostic systems that are sensitive, robust, portable, low-cost, and can accurately quantify multiple molecular targets in parallel, would have a tremendous impact in biomedical research and molecular diagnostics. In this application, we propose to use a magnetic nanosensor technology, in conjunction with a portable magnetic relaxometer, to develop a sensitive diagnostic test for intracellular pathogens and toxins in clinical samples. Bacterial infections are on the rise in the United States and their economic impact on the healthcare sector is significant. The presence of enterohemorrhagic E. coli O157:H7 in tainted produce, the B. anthracis attacks in 2001, and the recent identification of drug resistant Mycobacterium tuberculosis have sparked public concern and underscore the need to develop sensitive and portable diagnostic technologies for fast and accurate detection of bacteria and toxins in food and clinical samples. Our approach utilizes """"""""magnetic relaxation nanoswitches"""""""" (MRnS), i.e. magnetic nanoparticles that selectively change the spin-spin relaxation times (T2) of surrounding water molecules (NMR signal) upon specific molecular target interaction. The principal investigator of this grant application has previously shown that this technology can detect oligonucleotides in the femtomolemole range with extremely high molecular specificity [Nature Biotech. 2002;20:816-820], as well as other molecular targets such as proteins and viruses, without the need of target amplification. Most recently, we have developed magnetic nanosensors for the detection of a particular bacterium in blood and milk [Nanoletters 2007;7, 380]. Also, with collaborators at the Army's Edgewood Chemical and Biological Center, we have gathered preliminary data to detect ricin toxin, using magnetic nanosensors. As a detector, we have used a newly developed minituarized and portable NMR relaxometer that allows substantial improvement in detection threshold and speed. The overall goal of this application is to extend research on magnetic nanosensors in an effort to develop highly sensitive, minituarized and portable detection systems to screen for the presence of a particular bacterium and toxin in clinical samples. We hypothesize that our magnetic nanoparticle system can provide a single homogeneous assay that can be used to detect the presence of intracellular pathogens and toxins in blood, without the need for target amplification. As an intracellular bacterial pathogen model, we will use Mycobacterium avium spp. paratuberculosis (MAP). As a toxin model, we will use anthrax toxin (AT), which is produced by another intracellular pathogen;B. anthracis.
In this project, we will develop a diagnostic technology that merges the use of magnetic nanoparticles and a miniaturized detector to monitor the presence of an intracellular pathogen and toxin in clinical samples. This technology could facilitate quick, selective and sensitive bacterial detection to support clinical decision making.
|Santiesteban, Oscar J; Kaittanis, Charalambos; Perez, J Manuel (2014) Identification of toxin inhibitors using a magnetic nanosensor-based assay. Small 10:1202-11|
|Santra, Santimukul; Jativa, Samuel D; Kaittanis, Charalambos et al. (2012) Gadolinium-encapsulating iron oxide nanoprobe as activatable NMR/MRI contrast agent. ACS Nano 6:7281-94|
|Kaittanis, Charalambos; Santra, Santimukul; Asati, Atul et al. (2012) A cerium oxide nanoparticle-based device for the detection of chronic inflammation via optical and magnetic resonance imaging. Nanoscale 4:2117-23|
|Santiesteban, Oscar J; Kaittanis, Charalambos; Perez, J Manuel (2012) Assessment of molecular interactions through magnetic relaxation. Angew Chem Int Ed Engl 51:6728-32|
|Asati, Atul; Lehmkuhl, David; Diaz, Diego et al. (2012) Nanoceria facilitates the synthesis of poly(o-phenylenediamine) with pH-tunable morphology, conductivity, and photoluminescent properties. Langmuir 28:13066-71|
|Kaittanis, Charalambos; Boukhriss, Hamza; Santra, Santimukul et al. (2012) Rapid and sensitive detection of an intracellular pathogen in human peripheral leukocytes with hybridizing magnetic relaxation nanosensors. PLoS One 7:e35326|
|Santra, Santimukul; Kaittanis, Charalambos; Santiesteban, Oscar J et al. (2011) Cell-specific, activatable, and theranostic prodrug for dual-targeted cancer imaging and therapy. J Am Chem Soc 133:16680-8|
|Kaittanis, Charalambos; Banerjee, Tuhina; Santra, Santimukul et al. (2011) Identification of molecular-mimicry-based ligands for cholera diagnostics using magnetic relaxation. Bioconjug Chem 22:307-14|
|Santra, Santimukul; Perez, J Manuel (2011) Selective N-alkylation of ?-alanine facilitates the synthesis of a poly(amino acid)-based theranostic nanoagent. Biomacromolecules 12:3917-27|
|Kaittanis, Charalambos; Santra, Santimukul; Santiesteban, Oscar J et al. (2011) The assembly state between magnetic nanosensors and their targets orchestrates their magnetic relaxation response. J Am Chem Soc 133:3668-76|
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