The ‘Swiss army knife’ of antibacterials

Bacterial biofilms—clusters of microorganisms that form a sticky protective surface—are particularly challenging infections to treat. Their slimy outer layer provides protection from the host immune system, while the enclosed community creates an ideal ecosystem to generate multidrug resistance.

A team led by Biao Dong and Lin Wang at Jilin University and Jong Seung Kim of Korea University has developed a multipronged material approach to tackling biofilm infections in wounds (Angew. Chem., Int. Ed. 2024, DOI: 10.1002/anie.202319690). The solution is a nanocomposite that combines two established modes of antibacterial action—iron depletion therapy and photodynamic therapy—to achieve a greater killing effect than either method alone.

“One way to describe it is as a Swiss army knife,” says Vincent Rotello, a bionanochemist who develops nanotherapeutics for biofilm infections at the University of Massachusetts Amherst and is not affiliated with the research. “They’ve put a bunch of functions inside this material and as they add each one, it becomes more and more effective. It’s this combination that’s the interesting and novel aspect.”

Bacterial metabolism requires a steady stream of Fe³⁺, without which the cells die.

The team’s nanocomposite agent (which the researchers call Ga-CP@T) contains a close structural mimic of the iron-binding hemin porphyrin, which usually delivers this vital nutrient but with gallium ions in place of iron. Bacteria are unable to distinguish between these two similar ions, but gallium is redox inactive, meaning that bacteria can’t use it in metabolic processes. As the material releases Ga³⁺, it brings in Fe³⁺, sequestering the iron—which has a stronger binding affinity with the porphyrin—and leading to bacterial iron starvation.

At the same time, the nanocomposite also acts as a photodynamic therapeutic agent. When irradiated with long-wavelength light, the porphyrin catalyzes the formation of reactive oxygen species that damage surrounding cells, augmenting the antibacterial performance.

Rotello says that the early in vivo results are a promising start but that a higher potency will be required before the treatment is ready to move to the clinic. “It would also be very nice if they were able to do resistance-development studies. That’s one of the huge limitations now with antibiotics, so it’s a big question for this system,” he says.