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also reduced the presence of inflammatory immune cells, called eosinophils, which contribute to airway obstruction. “Not only did we see a substantial reduction of asthma phenotypes in our mouse model, but we tested the GATA3 DNAzyme-NANs in human white blood cells and saw both uptake of the nanoparticles and knock-down of expression of the gene of interest. This combination of data makes me really hopeful about the translational potential of the nanoparticles for human health,” says Szczepanek. Rouge points out another important detail: “Generally speaking, when putting nanoparticles in our lungs, you might think they could cause inflammation. However, we were really excited that at doses we used, the nanocarrier alone didn’t cause inflammation.”
“I believe our unique nanoconstruct holds great promise in the field of oligonucleotide delivery,” says Sawant. “I am happy to be a part of this collaborative research as it marks the beginning of the development of the NAN as an effective in vivo nanocarrier.” Rouge says the next step is to hopefully get NIH funding to continue the research: “We want to figure out where these nanocapsules go? We need to do a biodistribution study and other logical next steps, like pharmacokinetics and determining how long these therapeutics last in an organism.” The researchers were recently awarded a patent for the nanocapsule formulation, and they hope to commercialize it. Szczepanek explains the team envisions that, eventually, the technology could be delivered to the patient via an
inhaler, like current asthma medications are and, depending on exactly how it is formulated, that it could target active inflammation or act as a prophylactic measure. Rouge adds that this technology has the potential to be customizable saying, “The major theme is that different people respond differently to diseases in general, so there is the potential for personalized medicine. We are looking toward a paradigm shift because if you know the genetics of somebody in terms of the intensity or overexpression of a particular gene or if it is upregulated, we could treat it or at least depress it.”
Fusing Engineering and Precision Medicine with 3-D Tumor Model from UConn Today
What if we thought about our bodies as onto animal models. This allows them to see how the drug interacts with healthy materials? cells as well as the tumor. However, it This is the question Associate Professor comes with its own set of challenges, Kazunori Hoshino in the Department including cost, time, and ethical considof Biomedical Engineering raises in an- erations. alyzing three-dimensional (3-D) tumor To address these issues, Hoshino’s apmodels to test potential cancer drugs. proach uses a 3-D model of a tumor This technology will help bridge the in-vitro that can show how drugs will gap between in-vitro – or petri dish – act in-vivo without the need of animal testing and human subject testing for models. cancer drug development while cutting out the need for animal models by ap- “Testing an in–vitro model that mimics plying engineering methods to medical a tumor, rather than using animal models, is a recent trend in cancer studies,” research. Hoshino says. “However, the question to Currently, cancer drugs are first tested me was: can we create a proper analytion two-dimensional monolayers of cell cal method to study such a model?” cultures. While this is a necessary step in testing drugs, many drugs that are suc- Hoshino’s method uses materials scicessful at this stage fail when they get to ence concepts to test the tumor like a more advanced animal or human trials. material. Specifically, he tests for stiffness, or elasticity, a commonly tested Next, scientists graft human tumor cells property in engineered materials. 19
“If you’re creating a new material, you need to know the properties,” Hoshino says. Hoshino hypothesizes that tumors will have different levels of stiffness. Scientists do know tumors have different properties from healthy tissue — often being significantly stiffer, for instance. One possible reason for this stiffness is increased collagen production in tumors. They suspect this stiffness may protect the tumor by preventing drugs from reaching it. Hoshino’s method uses a series of polymer “chopsticks.” These chopsticks have a specific, known stiffness, designated by number. If they bend, it indicates the tumor is stiffer than that number. Read the full story at UConn Today
UConn Institute of Materials Science
