Mixed-surface polyamidoamine polymer variants retain nucleic acid-scavenger ability with reduced toxicity.

Journal Article (Journal Article)

Nucleic acid-binding polymers can have anti-inflammatory properties and beneficial effects in animal models of infection, trauma, cancer, and autoimmunity. PAMAM G3, a polyamidoamine dendrimer, is fully cationic bearing 32 protonable surface amines. However, while PAMAM G3 treatment leads to improved outcomes for mice infected with influenza, at risk of cancer metastasis, or genetically prone to lupus, its administration can lead to serosal inflammation and elevation of biomarkers of liver and kidney damage. Variants with reduced density of cationic charge through the interspersal of hydroxyl groups were evaluated as potentially better-tolerated alternatives. Notably, the variant PAMAM G3 50:50, similar in size as PAMAM G3 but with half the charge, was not toxic in cell culture, less associated with weight loss or serosal inflammation after parenteral administration, and remained effective in reducing glomerulonephritis in lupus-prone mice. Identification of such modified scavengers should facilitate their development as safe and effective anti-inflammatory agents.

Full Text

Duke Authors

Cited Authors

  • Olson, LB; Hunter, NI; Rempel, RE; Yu, H; Spencer, DM; Sullenger, CZ; Greene, WS; Varanko, AK; Eghtesadi, SA; Chilkoti, A; Pisetsky, DS; Everitt, JI; Sullenger, BA

Published Date

  • December 22, 2022

Published In

Volume / Issue

  • 25 / 12

Start / End Page

  • 105542 -

PubMed ID

  • 36444294

Pubmed Central ID

  • PMC9700028

Electronic International Standard Serial Number (EISSN)

  • 2589-0042

Digital Object Identifier (DOI)

  • 10.1016/j.isci.2022.105542


  • eng

Conference Location

  • United States