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Fabrication of Self-assembling Antimicrobial Nanofibers Via Peptide Self-assembly

September 28, 2018 | 11:00 a.m.
NH 203 | Seminar Flyer

Seminar Speaker

He Dong, Ph.D.

Associate Professor, Department of Chemistry and Biochemistry, The University of Texas at Arlington

Abstract: Coupled with the existence of biological threat agents engineered to be impervious to treatment, the full range of antibiotic-resistant microbes found in hospitals and the broader environment represent a “clear and present danger” to the general public, first responders, and military personnel. Effective response to this public health challenge necessitates adoption of an “outside-the-box” strategy for the de novo design of novel classes of microbicides. Antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics due to their direct targeting of bacterial cell membranes, which are less prone to modification to avoid the action of bactericides. However, their widespread use and translation into clinical application is hampered by the moderate to severe hemolytic activity and cytotoxicity.

My lab developed a novel self-assembling antimicrobial nanofiber (SAAN) technology for safer and more effective therapeutic administration of AMPs compared to conventional treatment options. SAANs, the “nucleus” of our antimicrobial therapeutic platform, are supramolecular assemblies of de novo designed AMPs that undergo programmed self-assembly into nanostructured fibers to “punch holes” in the bacterial membrane, thus killing the bacterial pathogen. The mode of antimicrobial action of SAANs have been thoroughly investigated and confirmed using transmission electron microscopy and solid-state NMR spectroscopy provided compelling spectroscopic and microscopic evidence that self-assembled nanofibers were physically in contact with bacterial cells causing local membrane deformation and rupture. While effectively killing bacteria, SAANs, owing to their nanoparticulate nature, were found to cross mammalian cell membranes harmlessly with greatly reduced membrane accumulation and possess exceptional cytocompatibility and hemocompatibility compared to natural AMPs. Through these systematic investigations, we expect to establish this new paradigm for the customized design of SAANs that will provide exquisite, tunable control of both bactericidal activity and cytocompatibility and can potentially overcome the drawbacks of traditional AMPs.

Bio: He Dong jointed UT Arlington in Jan 2018 as an Associate Professor. Prior to this position, she was as an Assistant Professor in the Department of Chemistry and Biomolecular Science at Clarkson University. He Dong obtained a PhD degree in organic chemistry at Rice University in 2008 where she focused on the self-assembly of nanostructured peptides into 3-D scaffolds for tissue regeneration. From 2008-2009, she was a postdoctoral researcher in Prof. Elliot Chaikof lab at Emory University focusing on anti-inflammatory peptide drug development. She continued her postdoctoral research from 2009 to 2012 in Prof. Ting Xu group at the University of California, Berkeley where she developed self-assembled hybrid peptide-polymer conjugates as long-circulating nanocarriers for cancer therapy. He Dong’s research spans from chemistry, materials science to biomedical sciences. Currently her primary research interests lie in the construction of biomaterials based on the self-assembly of peptides/proteins and block-copolymers for a wide range of biomedical applications including drug delivery, gene/siRNA delivery, vaccine delivery and antimicrobial therapy development He Dong is currently a member of the American Chemical Society, American Physical Society, Materials Research Society and biomedical Science Society. He Dong is a recipient of NSF Faculty Early Career Award and was recently featured as an emerging investigator in the Journal of Materials Chemistry B. He Dong obtained her PhD degree in organic chemistry at Rice University in 2008. After postdoc work at Emory University and the University of California at Berkeley, she started her independent career in the Department of Chemistry and Biomolecular Science at Clarkson University in 2012. She joined the Department of Chemistry and Biochemistry at the University of Texas at Arlington in 2018. Her research is focused on biomimetic design and supramolecular assembly of soft matter nanomaterials for anticancer and antimicrobial therapy development. She received a NSF Early Career Award for her work on the design and self-assembly of antimicrobial peptides.