title: Bundling and aggregation of DNA by cationic dendrimers.
abstract: Dendrimers are unique synthetic macromolecules of nanometer dimensions with a highly branched structure and globular shape. Among dendrimers, polyamidoamine (PAMAM) have received most attention as potential transfection agents for gene delivery, because these macromolecules bind DNA at physiological pH. The aim of this study was to examine the interaction of calf-thymus DNA with several dendrimers of different compositions, such as mPEG-PAMAM (G3), mPEG-PAMAM (G4), and PAMAM (G4) at physiological conditions, using constant DNA concentration and various dendrimer contents. FTIR, UV-visible, and CD spectroscopic methods, as well as atomic force microscopy (AFM), were used to analyze the macromolecule binding mode, the binding constant, and the effects of dendrimer complexation on DNA stability, aggregation, condensation, and conformation. Structural analysis showed a strong dendrimer-DNA interaction via major and minor grooves and the backbone phosphate group with overall binding constants of K(mPEG-G3) = 1.5 (±0.5) × 10(3) M(-1), K(mPEG-G4) = 3.4 (±0.80) × 10(3) M(-1), and K(PAMAM-G4) = 8.2 (±0.90) × 10(4) M(-1). The order of stability of polymer-DNA complexation is PAMAM-G4 > mPEG-G4 > mPEG-G3. Both hydrophilic and hydrophobic interactions were observed for dendrimer-DNA complexes. DNA remained in the B-family structure, while biopolymer particle formation and condensation occurred at high dendrimer concentrations.
authors.affiliation: Department of Chemistry-Biology, University of Québec at Trois-Rivières, Trois-Rivières, Québec, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Froehlich
authors.forename: J S
authors.initials: JS
authors.lastname: Mandeville
authors.forename: C M
authors.initials: CM
authors.lastname: Weinert
authors.forename: L
authors.initials: L
authors.lastname: Kreplak
authors.forename: H A
authors.initials: HA
authors.lastname: Tajmir-Riahi
mesh_terms: D000818:Animals; D002412:Cations / Q000138:chemical synthesis / Q000737:chemistry; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D002412:Cations; D050091:Dendrimers; C531249:Poly(amidoamine); D011073:Polyamines; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D004247:DNA; C427203:calf thymus DNA