Contribution of hydrophobicity, DNA and proteins to the cytotoxicity of cationic PAMAM dendrimers

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In most articles, cytotoxicity of cationic polyamidoamine (PAMAM) dendrimers toward red blood cells has been exclusively explained by their surface charge. We have focused on dendrimer hydrophobicity as a second possible factor that determines this cytotoxicity. Using PAMAM-NH2 dendrimers from the 3rd to the 6th generations and PAMAM-NH2-C12(25%) dendrimer of the 4th generation bearing 25% acyl groups, these induced hemolysis that increased with their surface charge and hydrophobicity. Interaction of PAMAM-NH2-C12(25%) G4 dendrimer with blood proteins (γ-globulin, α-thrombin, human serum albumin) and calf thymus DNA (ctDNA) significantly reduced their cytotoxicity toward red blood cells.

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