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Updated: Apr 30, 2026

Synthesis, Cellular Delivery and In vivo Application of Dendrimer-based pH Sensors
Published on: September 10, 2013
Nitric oxide-releasing quaternary ammonium-modified poly(amidoamine) dendrimers as dual action antibacterial agents
Brittany V Worley1, Danielle L Slomberg, Mark H Schoenfisch
1Department of Chemistry, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
Abstract:
Herein we describe the synthesis of nitric oxide (NO)-releasing quaternary ammonium (QA)-functionalized generation 1 (G1) and generation 4 (G4) poly(amidoamine) (PAMAM) dendrimers. Dendrimers were modified with QA moieties of different alkyl chain lengths (i.e., methyl, butyl, octyl, dodecyl) via a ring-opening reaction. The resultant secondary amines were then modified with N-diazeniumdiolate NO donors to yield NO-releasing QA-modified PAMAM dendrimers capable of spontaneous NO release (payloads of ~0.75 μmol/mg over 4 h). The bactericidal efficacy of individual (i.e., non-NO-releasing) and dual action (i.e., NO-releasing) QA-modified PAMAM dendrimers was evaluated against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa bacteria. Bactericidal activity was found to be dependent on dendrimer generation, QA alkyl chain length, and bacterial Gram class for both systems. Shorter alkyl chains (i.e., methylQA, butylQA) demonstrated increased bactericidal activity against P. aeruginosa versus S. aureus for both generations, with NO release markedly enhancing overall killing.
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