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Adv Mater. 2017 Sep;29(35). doi: 10.1002/adma.201701527. Epub 2017 Jul 12.

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

Author information

1
Koch Institute for Integrative Cancer Research and Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
2
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA, 92093, USA.
3
Dipartimento di Scienze e Tecnologie Chimiche, University of Rome, Tor Vergata, Via della Ricerca Scientifica, Rome, 00133, Italy.
4
Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
5
Koch Institute for Integrative Cancer Research, Institute for Medical Engineering and Science, Harvard-MIT Division of Health Sciences and Technology, Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
6
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Abstract

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.

KEYWORDS:

bacteria; lung infections; nanoparticles; peptides

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