title: Polycationic Nanofibers for Nucleic Acid Scavenging.
abstract: 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.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Jackman
authors.forename: Hemraj
authors.initials: H
authors.lastname: Juwarker
authors.forename: Luke P
authors.initials: LP
authors.lastname: Poveromo
authors.forename: Howard
authors.initials: H
authors.lastname: Levinson
authors.affiliation: Department of Biomedical Engineering, Columbia University , New York, New York, United States.
authors.forename: Kam W
authors.initials: KW
authors.lastname: Leong
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Sullenger
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D008298:Maleates / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D016688:Mice, Inbred NOD; D057139:Nanofibers / Q000008:administration & dosage / Q000737:chemistry*; D009696:Nucleic Acids / Q000737:chemistry; D011073:Polyamines / Q000008:administration & dosage / Q000737:chemistry; D000071228:Polyelectrolytes; D011137:Polystyrenes / Q000008:administration & dosage / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000472:pathogenicity; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D004317:Doxorubicin; D004337:Drug Carriers; D008298:Maleates; D009696:Nucleic Acids; D011073:Polyamines; D000071228:Polyelectrolytes; D011137:Polystyrenes; C520889:poly(styrene-alt-maleic anhydride)