Effect of poly(amidoamine) dendrimers on the structure and activity of immune molecules
Effect of poly(amidoamine) dendrimers on the structure and activity of immune molecules
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聚酰胺胺树枝状聚合物对免疫分子结构和活性的影响
DOI：
10.1016/j.bbagen.2014.11.016
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发表时间：
2015-02-01
影响因子：
3
通讯作者：
Qiu, Xiaozhong
中科院分区：
文献类型：
--
作者：
Lin, Jiansheng;Hua, Wenxi;Qiu, Xiaozhong
背景资料：聚酰胺-胺（PAMAM）树枝状大分子是一种用途广泛的生物医用高分子材料，在药物载体、基因载体、造影剂等方面有着广泛的应用。在这些生物医用材料中，PAMAM树枝状大分子的生物安全性是一个关键问题，它不仅影响到其对宿主的毒性，而且影响到材料预期的体内生物功能。为了阐明PAMAM树枝状大分子的生物安全性，本工作探讨了含胺、羟基和羧基的第5代PAMAM树枝状大分子对免疫分子的影响.方法：采用紫外-可见光谱、荧光光谱和圆二色光谱研究了PAMAM树枝状大分子对免疫分子γ-球蛋白二级结构和构象的影响.通过酶联免疫吸附试验测定PAMAM树枝状聚合物对补体活化的影响。结果：PAMAM树枝状大分子能影响γ-球蛋白的二级结构和构象，抑制补体激活。第5代PAMAM树枝状大分子的羧基在10 mg/mL受损的红细胞（RBC）抗原抗体reaction.Conclusions：从这些结果来看，PAMAM树枝状大分子对免疫分子的影响取决于其本体结构和表面基团。一般意义：这项工作提供了重要的信息，为PAMAM树枝状大分子的免疫相容性评价，临床前设计和临床应用。(C)2014爱思唯尔有限公司版权所有。
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.