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              Research

 

                        - Molecular Diagnostics

 

                              Bacterial detection      Bacterial drug resistance assessment               

                              Toxin detection      Cancer biomarker detection

 

                        - Molecular Imaging

 

                              Cancer imaging  

 

                        - Nanoparticle Technologies

 

                              Multifunctional  nanoparticles

                              Catalytic and antioxidant nanoparticles           

                   

                        - Functional Nanocomposites

 

                              Advanced functional nanomaterials

                              Enhanced supramolecular matrices   

 

 

Bacterial detection:

 

Advanced functional nanomaterials: Nanomaterials, due to their enhanced properties, can be the building blocks of functional nanocomposites having numerous applications, ranging from electronics to prosthetic devices. In our lab, we synthesize nanomaterials with tunable cores and coatings, which can be further functionalized with various small molecules and ligands via facile chemical methods. These nanomaterials can have a plethora of selected properties, including superparamagnetism, luminescence, fluorescence, radio-opacity, selective antioxidant activity, enzymatic activity, protein conjugating linkers, and guest payload cavities. 

Enhanced supramolecular matrices: Our future aim is to utilize these nanomaterials for the formation of enhanced supramolecular matrices, which can have properties deriving from the combinatorial incorporation of various nanoscale building blocks. We intend to study how the organized formation of these supramolecular matrices and delineate the factors governing this process, such as the temperature, the nature of the nanoparticles’ functional groups, surface charge, coating and cores. (Back to top)

Current efforts in our laboratory involve the development of biocompatible polymer-coated cerium oxide nanoparticles (nanoceria). We have found that our polymer-coated nanoceria possess autocatalytic behavior and  are potent antioxidants that scavenge a variety of reactive oxygen species. Interestingly, our lab discovered that the antioxidant activity of nanoceria is pH-dependent. Specifically, at physiological pH (pH ~ 7) the nanoparticles behave as free radical scavengers, whereas in acidic microenvironments (pH ~ 4), such as the one found in tumors, the nanoparticles lose their antioxidant activity. In a recent publication, we demonstrated that nanoceria can provide selective cytoprotection against free radical insults, by protecting normal non-transformed cells whereas at the same allowing the free radicals to cause irreversible damage and cytotoxicity to cancer cells. Current work aims to elucidate the pH-dependent cytoprotection mechanism of nanoceria, using material synthesis, chemical and biochemical techniques. (Back to top)

Polymeric nanoparticles: Our lab designs and synthesizes novel polymeric nanoparticles suitable for targeted imaging and drug delivery. These nanoparticles are composed of a biodegradable polymeric coating and can efficiently co-encapsulate organic fluorophores and therapeutic agents (for instance, hydrophobic anti-neoplastic agents). The surface of the nanoparticles can be readily modified, allowing the facile conjugation of targeting moieties that promote enhanced specific uptake by the tumor. Overall, this research will help the optimization of therapeutic regimes, as the nanoparticles’ can provide spatiotemporal information about their in vivo distribution, the drug’s homing and the tumor regression.

Iron oxide nanoparticles: Recently, we have developed multifunctional iron oxide nanoparticles that can be used in cancer therapeutics. Specifically, we have developed novel methods to synthesize iron oxide nanoparticles, containing near-infrared fluorescent dyes and anticancer drugs. These nanoparticles apart from being excellent MRI contrast agents are fluorescent and can deliver their therapeutic load with high specificity.  (Back to top)

In the field of molecular imaging, our group aims the development of mutimodal imaging modalities for cancer imaging. Specifically, we design biodegradable soft polymeric or polymer-coated fluorophore-encapsulating iron oxide nanoparticles for the targeted in vitro and in vivo imaging of cancer cells and tumoric lesions. These nanoparticles possess limited cytotoxicity, are stable in buffer solutions, and can be used for MRI, or near-infrared imaging using fluorescence molecular tomography. (Back to top)    

 In another area of molecular diagnostics, our group is interested in the early diagnosis of cancer. Utilizing iron oxide nanoparticles, we were able to assess the levels and enzymatic activity of telomerase, a key oncogene that is upregulated in most tumors leading to their immortalization due to aberrant continuous maintenance of the chromosomal telomeric repeats. Currently, we develop magnetic nanosensors that can detect and quantify multiple tumor biomarkers in blood, utilizing magnetic relaxation methods. (Back to top)    

Apart from detecting the presence of microorganisms, our group is interested in the determination of these pathogens’ susceptibility to antibiotic agents. Utilizing either gold or iron oxide nanoparticles, we can assess bacterial drug resistance and identify the minimum inhibitory concentration (MIC) of an effective antibiotic within a couple of hours without compromising reliability. We are able to achieve this by developing nanosensors that can monitor the bacterial metabolic activity, through the levels of free complex carbohydrates in the growing medium. Our assays outperform the turbidity method, the gold standard microbiological assay for MIC determination, which provides results within 24 hours. Additionally, as the turbidity method is not effective in opaque media, we used iron oxide nanoparticles to rapidly and reliably assess MIC in blood. Current efforts are geared towards the development of more robust assays, portable devices and the screening of novel antimicrobial agents. (Back to top)

Bacterial intoxication is still a major source of bacterial pathogenesis. Apart from the potential use of toxins as bioterrrorism agents, toxins can cause widespread epidemics upon entering the food distribution chain. Contaminated produce, such as spinach and tomatoes, as well as dairy products and meat, can cause severe illness, and even death, to many individuals. Utilizing magnetic nanosensors, we target the development of toxin-specific nanosenors that can determine the presence of a particular toxin in environmental, food, and clinical samples. (Back to top)

Our laboratory is actively developing magnetic nanosensors for the rapid detection of microbiological agents in complex media. Specifically, our group has reported the sensitive detection of bacteria (Mycobacterium avium spp. paratuberculosis – MAP) in milk and blood within 30 minutes, using dextran-coated iron oxide nanoparticles conjugated with antibodies that recognize surface proteins found on the bacteria. With this technology, we can potentially detect a single bacterium  (1 - 10  CFU), under interference introduced by the presence of six different bacterial species (109 CFU). As MAP causes Johne’s disease in cattle, each year causing billion dollar losses to the US agriculture, and as this microorganism has been implicated in the etiology of Crohn’s disease, our technology can have applications spanning a wide spectrum of economic activities, ranging from agriculture to healthcare, and from food industry to homeland security. Current projects target the development of magnetic nanosensors that can detect bacterial toxins in environmental samples, as well as bacterial antigens in circulation. (Back to top)

 

 

 

 

 

 

 

 

 

 

 

 

 

Toxin detection:

 

 

 

 

 

 

 

 

 

 

 

Bacterial drug resistance assessment:

 

Functional nanocomposites:

 

 

Bifunctional catalytic and antioxidant nanoparticles:

 

 

Multifunctional and multimodal nanoparticles for imaging, sensing, and targeted therapy:

 

 

Cancer imaging:

 

 

Cancer biomarker detection: