Advanced Materials
Advanced Materials
5 years ago

Porous Silicon Nanoparticle Delivery of Tandem Peptide Anti-Infectives for the Treatment of Pseudomonas aeruginosa Lung Infections

Porous Silicon Nanoparticle Delivery of Tandem Peptide Anti-Infectives for the Treatment of Pseudomonas aeruginosa Lung Infections
Erkki Ruoslahti, Francesco Ricci, Sangeeta N. Bhatia, Matthew Skalak, Michael J. Sailor, Alessandro Bertucci, Gary Braun, Ester J. Kwon
There is an urgent need for new materials to treat bacterial infections. In order to improve antibacterial delivery, an anti-infective nanomaterial is developed that utilizes 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. First, a library of antibacterial peptides is screened that combines a membrane-localizing peptide with a toxic peptide cargo and discovers a tandem peptide that displays synergy between the two domains and is able to kill Pseudomonas aeruginosa at sub-micromolar concentrations. To apply this material to the lung, the tandem peptide is loaded into porous silicon nanoparticles (pSiNPs). Charged peptide payloads are loaded into the pores of the pSiNP at ≈30% mass loading and ≈90% loading efficiency using phosphonate surface chemistry. When delivered to the lungs of mice, this anti-infective nanomaterial exhibits improved safety profiles over free peptides. Moreover, treatment of a lung infection of P. aeruginosa results in a large reduction in bacterial numbers and markedly improves survival compared to untreated mice. Collectively, this study presents the selection of a bifunctional peptide-based anti-infective agent and its delivery via biodegradable nanoparticles for application to an animal model of lung infection. Antibiotic treatment can benefit from strategies to improve localization. A membrane-localizing anti-infective peptide is delivered via biodegradable porous silicon nanoparticles to decrease bacterial numbers in a lung infection model. It is believed that these tandem peptide nanomaterials offer an approach to building anti-infectives that could complement existing small-molecule antibiotic treatments.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/adma.201701527

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.