Polycationic Nanofibers for Nucleic Acid Scavenging.

Published

Journal Article

Dying cells release nucleic acids (NA) and NA-containing complexes that activate inflammatory pathways of immune cells. Sustained activation of these pathways contributes to chronic inflammation frequently encountered in autoimmune and inflammatory diseases. In this study, grafting of cationic polymers onto a nanofibrous mesh enabled local scavenging of negatively charged pro-inflammatory molecules in the extracellular space. Nucleic acid scavenging nanofibers (NASFs) formed from poly(styrene-alt-maleic anhydride) conjugated with 1.8 kDa bPEI resulted in nanofibers of diameters 486 ± 9 nm. NASFs inhibited the NF-κB response stimulated by the negatively charged agonists, CpG and poly(I:C), in Ramos-blue cells but not Pam3CSK4, a nonanionic agonist. Moreover, NASFs significantly impeded NF-κB activation in cells stimulated with damage-associated molecular pattern molecules (DAMPs) released from doxorubicin killed cancer cells. In vivo application of NASFs to open wounds demonstrated nucleic acid scavenging in wounds of diabetic mice infected with Pseudomonas aeruginosa, suggesting the in vivo efficacy of NASFs. This simple technique of generating NASF results in effective localized anti-inflammation in vitro and local nucleic acid scavenging in vivo.

Full Text

Duke Authors

Cited Authors

  • Jackman, JG; Juwarker, H; Poveromo, LP; Levinson, H; Leong, KW; Sullenger, BA

Published Date

  • November 14, 2016

Published In

Volume / Issue

  • 17 / 11

Start / End Page

  • 3706 - 3713

PubMed ID

  • 27741396

Pubmed Central ID

  • 27741396

Electronic International Standard Serial Number (EISSN)

  • 1526-4602

Digital Object Identifier (DOI)

  • 10.1021/acs.biomac.6b01236

Language

  • eng

Conference Location

  • United States