Jiansheng Lin1, Wenxi Hua1, Yi Zhang2, Chenghua Li2, Wei Xue2, Jian Yin3, Zonghua Liu4, Xiaozhong Qiu5. 1. Department of Anatomy, Key Laboratory of Construction and Detection of Guangdong Province, Southern Medical University, Guangzhou 510515, China. 2. Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China. 3. Department of Anatomy, Hunan University of Chinese Medicine, Changsha 410208, China. 4. Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China. Electronic address: tliuzonghua@jnu.edu.cn. 5. Department of Anatomy, Key Laboratory of Construction and Detection of Guangdong Province, Southern Medical University, Guangzhou 510515, China. Electronic address: qiuxzh@aliyun.com.
Abstract
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 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. RESULTS: 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. 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.
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 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. RESULTS: 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. 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.
Authors: Srinivas Abbina; Chanel C La; Sreeparna Vappala; Manu Thomas Kalathottukaren; Usama Abbasi; Arshdeep Gill; Stephanie A Smith; Charles A Haynes; James H Morrissey; Jayachandran N Kizhakkedathu Journal: Mol Pharm Date: 2022-05-02 Impact factor: 5.364
Authors: Lin-Ping Wu; Mario Ficker; Jørn B Christensen; Dmitri Simberg; Panagiotis N Trohopoulos; Seyed M Moghimi Journal: Nat Commun Date: 2021-08-11 Impact factor: 14.919