Effect of poly(amidoamine) dendrimers on the structure and activity of immune molecules

Background: Poly(amidoamine) (PAMAM) dendrimers are widely used biomedical polymers, which are extensively applied in drug delivery, gene delivery, contrast agent, etc. In these biomedical applications, the bio-safety of the PAMAM dendrimers is a critical issue, which affects not only their toxicity to the host but also the expected in vivo biofunctions of the materials. To clarify the bio-safety of PAMAM dendrimers, the effects of generation 5 PAMAM dendrimers with amine, hydroxyl or carboxyl groups on immune molecules were explored in this work. Methods: Specifically, the effect of the PAMAM dendrimers on the secondary structure and conformation of immune molecule gamma-globulin was studied by using ultraviolet-visible, fluorescence, and circular dichroism spectroscopies. The effect of the PAMAM dendrimers on complement activation was determined by enzyme-linked immunosorbent assay. Further, the effect of the PAMAM dendrimers on antigen-antibody reaction was studied by using human red blood cell agglutination assay. Results: The results showed that the PAMAM dendrimers could affect the secondary structure and conformation of gamma-globulin, and inhibited complement activation. Generation 5 PAMAM dendrimer with carboxyl group at 10 mg/mL impaired red blood cell (RBC) antigen-antibody reaction. Conclusions: From these results, the effects of the PAMAM dendrimers on immune molecules depend on their bulk structure and surface groups. General significance: This work provides important information for the immunocompatibility evaluation, preclinical design, and clinical applications of PAMAM dendrimers. (C) 2014 Elsevier B.V. All rights reserved.