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

• Published in: Biochimica et biophysica acta Vol. 1850; no. 2; pp. 419 - 425
• Main Authors: Lin, Jiansheng, Hua, Wenxi, Zhang, Yi, Li, Chenghua, Xue, Wei, Yin, Jian, Liu, Zonghua, Qiu, Xiaozhong
• Format: Journal Article
• Language: English
• Published: Netherlands 01.02.2015
• Subjects: agglutination; Antigen-Antibody Reactions; circular dichroism spectroscopy; complement; Dendrimers - chemistry; drugs; enzyme-linked immunosorbent assay; erythrocytes; Erythrocytes - chemistry; Erythrocytes - immunology; Female; fluorescence; gamma-globulins; gamma-Globulins - chemistry; gamma-Globulins - immunology; gene transfer; Humans; Male; polymers; Structure-Activity Relationship; toxicity; Biomedical material; Biocompatibility; Poly(amidoamine); Immunocompatibility
• ISSN: 0304-4165; 0006-3002
• DOI: 10.1016/j.bbagen.2014.11.016

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. Specifically, the effect of the PAMAM dendrimers on the secondary structure and conformation of immune molecule γ-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. The results showed that, the PAMAM dendrimers could affect the secondary structure and conformation of γ-globulin, and inhibited complement activation. Generation 5 PAMAM dendrimer with carboxyl group at 10mg/mL impaired red blood cell (RBC) antigen-antibody reaction. From these results, the effects of the PAMAM dendrimers on immune molecules depend on their bulk structure and surface groups. This work provides important information for the immunocompatibility evaluation, preclinical design, and clinical applications of PAMAM dendrimers.