In the Oct. 10 advance online edition of the journal Nature Materials, researchers describe how they encapsulated short pieces of RNA into engineered particles called thioketal nanoparticles and orally delivered the genetic material directly to the inflamed intestines of animals. The research was sponsored by the National Science Foundation and National Institutes of Health.
"The thioketal nanoparticles we designed are stable in both acids and bases and only break open to release the pieces of RNA in the presence of reactive oxygen species, which are found in and around inflamed tissue in the gastrointestinal tract of individuals with inflammatory bowel diseases," said Niren Murthy, an associate professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University.This work was done in collaboration with Emory University Division of Digestive Diseases professor Shanthi Sitaraman, associate professor Didier Merlin and postdoctoral fellow Guillaume Dalmasso.
In the paper, the thioketal nanoparticles were formulated from a new polymer -- poly-(1,4-phenyleneacetone dimethylene thioketal) (PPADT) -- and engineered to have a diameter of approximately 600 nanometers for optimal oral delivery.
For their experiments, the researchers used a mouse model of ulcerative colitis -- a debilitating inflammatory bowel disease in which the digestive tract becomes inflamed, causing severe diarrhea and abdominal pain that can lead to life-threatening complications.
The researchers orally administered thioketal nanoparticles loaded with siRNA that inhibits an inflammation-promoting cytokine called tumor necrosis factor - alpha (TNF-á). The nanoparticles traveled directly to the mouse colons where reactive oxygen species were being produced in excess and decreased the cytokine production levels there.
Tissue samples from the colons treated with siRNA delivered by these thioketal nanoparticles exhibited intact epitheliums, well-defined fingerlike "crypt" structures and lower levels of inflammation -- signs that the colon was protected against ulcerative colitis.
"Since ulcerative colitis is restricted to the colon, these results confirm that the siRNA-loaded thioketal nanoparticles remain stable in non-inflamed regions of the gastrointestinal tract while targeting siRNA to inflamed intestinal tissues," explained the paper's lead author Scott Wilson, a graduate student in the Georgia Tech School of Chemical & Biomolecular Engineering.
The paper showed that thioketal nanoparticles have the chemical and physical properties needed to overcome the obstacles of gastrointestinal fluids, intestinal mucosa and cellular barriers to provide therapy to inflamed intestinal tissues, he added.
The researchers are currently working on increasing the degradation rate of the nanoparticles and enhancing their reactivity with reactive oxygen species. The team also plans to conduct a biodistribution study to detail how the nanoparticles travel through the body.
"Polymer toxicity is something we'll have to investigate further, but during this study we discovered that thioketal nanoparticles loaded with siRNA have a cell toxicity profile similar to nanoparticles formulated from the FDA-approved material poly(lactic-co-glycolic acid) (PLGA)," added Murthy.
In the future, thioketal nanoparticles may become a significant player in the treatment of numerous gastrointestinal diseases linked to intestinal inflammation, including gastrointestinal cancers, inflammatory bowel diseases and viral infections, according to Murthy.
This project is supported by the National Science Foundation (NSF) (Award Nos. EEC-9731643 and NSF Career BES-0546962) and the National Institutes of Health (NIH) (Award Nos. UO1 HL80711-01, R21 EB006418, RO1 HL096796-01, RO1 DK071594, R01 DK064711 and T32 GM08433). The content is solely the responsibility of the principal investigator and does not necessarily represent the official views of the NSF or NIH.
Abby Vogel Robinson | EurekAlert!
Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego
New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg
On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.
On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
27.02.2017 | Materials Sciences
27.02.2017 | Interdisciplinary Research
27.02.2017 | Life Sciences