AsianScientist (Dec. 12, 2013) – Researchers at Singapore’s A*STAR Institute of Bioengineering and Nanotechnology (IBN) and California’s IBM Research (IBM) have converted polyethylene terephthalate (PET), which is widely used to make plastic bottles, into a non-toxic biocompatible material with superior fungal killing properties.
As reported in Nature Communications, their new material proved particularly effective in destroying drug-resistant fungi and fungal biofilm, displaying great potential as an antifungal agent to prevent and treat topical fungus-induced diseases such as skin infections and keratitis.
In recent years, the number of opportunistic fungal infections has increased due to growing populations of patients with weakened immune systems, for example due to cancer, organ transplant or HIV/AIDS. Of great concern to the clinical and healthcare communities is the rise in fungal infections that are resistant to conventional antifungal drugs. These trends necessitate the urgent development of suitable alternatives to the limited selection of available antifungal agents.
A particular challenge facing researchers lies in fungi’s metabolic similarity to mammalian cells. Existing antifungal agents are unable to distinguish between infected and healthy cells, and frequently end up attacking the latter. Hence, patients commonly report hemolysis and nephrotoxicity as treatment side effects.
Leveraging on IBM’s polymer synthesis and computational expertise, as well as IBN’s nanomedicine and biomaterials research expertise, the researchers transformed PET, a common plastic material, into novel small molecule compounds that self-assemble in water into nanofibers.
The nanofibers self-assemble via electrostatic interaction and selectively target fungal cells and penetrate their membrane, killing them in the process.
“The ability of our molecules to self-assemble into nanofibers is important because unlike discrete molecules, fibers increase the local concentration of cationic charges and compound mass,” said Dr. Yi Yan Yang, group leader of IBN. “This facilitates the targeting of the fungal membrane and its subsequent lysis, enabling the fungi to be destroyed at low concentrations. The result is a highly efficient killing strategy that causes minimal damage or toxicity to surrounding healthy cells.”
In vitro studies conducted at IBN demonstrated that the nanofibers eradicated over 99.9 percent of C. albicans after just one hour of incubation and did not develop any drug resistance, even after 11 treatments.
The nanofibers were also used to effectively treat contact lens-associated fungal biofilm eye infection in mice without causing any toxicity to the eye. In comparison, the conventional antifungal drug, fluconazole, was only able to inhibit additional fungal growth, and the infection exhibited drug resistance after six treatments. Further, Fluconazole was not effective against biofilms.
“As computational predictive methodologies continue to advance, we can begin to establish ground rules for self-assembly to design complex therapeutics to fight infections, as well as the effective encapsulation, transport and delivery of a wide variety of cargos to their targeted disease sites,” said Dr. James Hedrick, an Advanced Organic Materials scientist at IBM Research.
The article can be found at: Fukushima K et al. (2013) Supramolecular high-aspect ratio assemblies with strong antifungal activity.
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