Nanoenvironment Research Activities
Microbial Biofilm Interactions with Nanoparticles
(A) ‘Biofilm’ infections form when bacteria attach to tissues and surround themselves within a protective matrix of EPS. Cells communicate with each other using diffusible chemical signals, a process called ‘quorum sensing’, which makes biofilms more resistant to antibiotics. (B) EPS binds and prevents soluble antibiotics from reaching cells. However, nanoparticle-bound antibiotics more-efficiently penetrate EPS to reach cells and potentially destroy them.
The research groups of Professors Alan Decho and Brian Benicewicz in the Departments of Environmental Health Sciences and Chemistry and Biochemistry, respectively, are investigating how nanoparticles interact with biofilms, microbial communities enveloped by an extracellular biopolymer called EPS. Biofilm-based infections are a major cause of antibiotic resistant, nosocomial, and persistent infections. The drug-resistant properties and metabolic pliancy of biofilms represent a substantial hurdle in the design of antimicrobial therapies for reducing infection outcomes. They believe nanoparticles represent a novel technology that may facilitate the penetration of antimicrobials into the EPS matrix to reach cells, and to potentially shut down quorum sensing within a biofilm. Their studies involve the design and testing of nanoparticles having novel surface chemistries to understand how biofilm, especially in pathogenic systems, may be better controlled or manipulated.
These researchers are using nanotechnology as ‘Antibiotic-Delivery Vehicles’ (ADVs) to help antibiotics penetrate the biofilm, reaching cells. In addition, ‘Chemical Signal Sponges’ (CSSs) are being developed to interfere with bacterial chemical communication-quorum sensing. They are being constructed using a novel RAFT chemistry that has been refined in the Benicewicz laboratory. Theoretically, each CSS-nanoparticle will be able to bind thousands of AHL signal molecules. Finally, the CSS-nanoparticles will be further designed to be ‘magnetic’, and hence can potentially be removed from the system (i.e. human body) by magnets. This would allow short exposures to antibiotics and significantly reduce chances of bacteria developing resistance mechanisms. This multi-pronged approach will allow for targeting bacteria cells, and the extracellular chemical communication networks; a process which allows bacteria to coordinate resistance activities within a biofilm.
Partitioning of Nanomaterials in Tidal Marsh Creeks
Professors John Ferry and Tim Shaw are studying how nanoparticles transfer from the water column into the food web.
This study used a series of mesocosms as laboratories for measuring the behavior of nanoparticles in complex environments. These systems are representative of tidal marsh creeks located along the South Carolina Coast and contained sea water, sediment, sea grass (Spartina alterniflora), northern quahog clams (aria mercenaria), mud snails (Ilyanassa obsolete), sheepshead minnows (Cyprinodon variegates) and grass shrimp (Palaemonetes pugio). Glass slides were also placed in the tanks for collection of microbial biofilms. Gold nanorods were added to the mesocosms for 12 days and partitioning of gold was monitored by inductively coupled plasma mass spectrometry for each phase and species. Results of this work show that on a per mass basis the filter feeders (clams) were the most effective sink for nanoparticles, followed closely by biofilms.
The article was recently published in Nature Nanotechnology (John L. Ferry, Preston Craig, Cole Hexel, Patrick Sisco, Rebecca Frey, Paul L. Pennington, Michael H. Fulton, I. Geoff Scott, Alan W. Decho, Shosaku Kashiwada, Catherine J. Murphy and Timothy J. Shaw. Transfer of gold nanoparticles from the water column to the estuarine food web. Nat Nanotechnol. 2009 Jul;4(7):441-4. Epub 2009 Jun 21. Read full details of this new study.
Modulation of immune-mediated signaling pathways by engineered nanoparticles
Scientists Tara Sabo-Attwood and Eugenia Ariza are investigating the immunomodulatory potential of nanoparticles in mammalian cells
The physiochemical properties of select engineered nanoparticles may allow them to interact with toll like receptors (TLRs) triggering a signaling pathway that activates a nuclear transcriptional factor NF- k B . NF-k B enters the nucleus binds to and activates genes modulating immune defense and inflammatory responses.
Researchers Sabo-Attwood and Ariza in the Arnold School of Public Health, Department of Environmental Health Sciences are investigating whether engineered nanoparticles (ENPs) have the potential to modulate the immune system. Activation of the immune system (i.e. inflammation) is a critical process associated with many human diseases and determining which properties of these particles contribute to this process is the goal of their work. The increased use of ENPs without the similar aggressive development of tools for determining their biological reactivity is a cause for concern. While it will be impossible to exhaustively study all properties of ENPs, some key characteristics of their biological behavior can be chosen as indicators of potential cytotoxicity for predicting in vivo health outcomes. ENP surface chemistry, aggregation state, and solubility may influence their ability to modulate immune defense and inflammatory responses in organisms. Specifically, ENPs may be recognized by Toll-Like Receptors (TLRs), triggering an immune response through the Nuclear Factor-kappa B (NF- k B) transcription factor. This immune regulating behavior of silver, gold and carbon nanotubes is currently being correlated with surface charge, degree of solubility, and aggregate formation. Ultimately, this work will lead to a better understanding of the potential immunomodulatory properties of nanoparticles and allow for the development of a high throughput screening method applicable to in vivo health effects.