Nanoparticle Treatment Cures Bacterial Infection in Model

A novel approach for treating bacterial infections is based on the use of porous silicon nanoparticles to transport a combination of bactericidal peptides, which penetrate the cell membranes of Gram-negative bacteria and kill them with minimal unpleasant side effects.

In order to improve antibacterial delivery, investigators at the Massachusetts Institute of Technology (Cambridge, MA, USA) developed an anti-infective nanomaterial that utilized two strategies for localization: i) a biodegradable nanoparticle carrier to localize therapeutics within the tissue, and ii) a novel tandem peptide cargo to localize payload to bacterial membranes.

The first step was to screen a library of antibacterial peptides that combined membrane-localizing peptides with toxic peptides. This screen identified a tandem peptide - the toxic peptide KLAKAK (lysine-leucine-alanine-lysine-alanine-lysine) and the transport peptide lactoferrin - that displayed synergy between the two domains and was able to kill Pseudomonas aeruginosa at sub-micromolar concentrations.

To apply this material to the lung, the tandem peptide was loaded into porous silicon nanoparticles (pSiNPs). Charged peptide payloads were loaded into the pores of the pSiNP at approximately 30% mass loading and approximately 90% loading efficiency using phosphonate surface chemistry.

The investigators reported in the July 12, 2017, online edition of the journal Advanced Materials that when delivered to the lungs of mice, this anti-infective nanomaterial was 30 times more effective at killing Pseudomonas aeruginosa than were the individual peptides administered without a carrier, and it was less toxic than the free peptides. Moreover, treatment of a lung infection of P. aeruginosa resulted in a large reduction in bacterial numbers and markedly improved survival compared to untreated mice.

This approach is modeled on a strategy that the investigators had previously used to deliver targeted cancer drugs. "There are a lot of similarities in the delivery challenges," said senior author Dr. Sangeeta Bhatia, professor of health sciences, technology and electrical engineering, and computer science at the Massachusetts Institute of Technology. "In infection, as in cancer, the name of the game is selectively killing something, using a drug that has potential side effects. We have adapted a lot of the same concepts from our cancer work, including boosting local concentration of the cargo and then making the cargo selectively interact with the target, which is now bacteria instead of a tumor."

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