Self assembling nanofibres made from waste plastic make new antifungal agents
2 January 2014
Researchers from IBM and the Institute of Bioengineering and Nanotechnology (IBN) in Singapore have converted common plastic materials like PET (polyethylene terephthalate) from old bottles into non-toxic and biocompatible materials to treat hard-to-cure fungal infections.
The research has been published in the journal Nature.com.
There is a lack of effective treatments for fungal infections, which range in severity from topical skin conditions like athlete's foot to life-threatening fungal blood infections. There is a pressing need to develop efficient and disease-specific antifungal agents to mitigate a growing drug resistance problem. Traditional antifungal therapeutics need to get inside the cell to attack the infection but have trouble targeting and penetrating the fungi membrane wall. Also, since fungi are metabolically similar to mammalian cells, existing drugs can have trouble differentiating between healthy and infected cells.
IBM scientists applied an organic catalytic process to facilitate the transformation of PET, or waste plastic from a bottle, into entirely new molecules that can be transformed into antifungal agents. This is significant as plastic bottles are typically recycled by mechanical grounding and can mostly be reused only in secondary products like clothes, carpeting or playground equipment.
These new antifungal agents self-assemble through a hydrogen-bonding process, sticking to each other like molecular Velcro in a polymer-like fashion to form nanofibres. The nanofibre carries a positive charge and can selectively target and attach to only the negatively-charged fungal membranes based on electrostatic interaction. It then breaks through and destroys the fungal cell membrane walls, preventing it from developing resistance.
According to Dr Yi Yan Yang, Group Leader, IBN, “The ability of these molecules to self-assemble into nanofibres is important because unlike discrete molecules, fibres increase the local concentration of cationic charges and compound mass. This facilitates the targeting of the fungal membrane and its subsequent lysis, enabling the fungi to be destroyed at low concentrations.”
Leveraging IBM Research’s computational capabilities, the researchers simulated the antifungal assemblies, predicting which structural modifications would create the desired therapeutic efficacy.
“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 diseased sites,” said Dr James Hedrick, Advanced Organic Materials Scientist, IBM Research – Almaden.
The minimum inhibitory concentration (MIC) of the nanofibres, which is the lowest concentration that inhibits the visible growth of fungi, demonstrated strong antifungal activity against multiple types of fungal infections. In further studies conducted by Singapore’s IBN, testing showed the nanofibres eradicated more than 99.9% of C. albicans, a fungal infection causing the third most common blood stream infection in the United States, after a single hour of incubation and indicated no resistance after 11 treatments. Conventional antifungal drugs were only able to suppress additional fungal growth while the infection exhibited drug resistance after six treatments
Additional findings of this research indicated the nanofibres effectively dispersed fungal biofilms after one-time treatment while conventional antifungal drugs were not effective against biofilms.
The in vivo antifungal activity of the nanofibres was also evaluated in a mouse model using a contact lens-associated C. albicans biofilm infection. The nanofibres significantly decreased the number of fungi, hindered new fungal structure growth in the cornea and reduced the severity of existing eye inflammation. These experiments also showed mammalian cells survived long after incubation with the nanofibres, indicating excellent in vitro biocompatibility. In addition, no significant tissue erosion is observed in the mouse cornea after topical application of the nanofibres.
“A key focus of IBN’s nanomedicine research efforts is the development of novel polymers and materials for more effective treatment and prevention of various diseases,” said Professor Jackie Y. Ying, IBN Executive Director. “Our latest breakthrough with IBM allows us to specifically target and eradicate drug-resistant and drug-sensitive fungi strains and fungal biofilms, without harming surrounding healthy cells.”