INSERM, U1043, CNRS, U5282, UPS, Centre de Physiopathologie de Toulouse-Purpan, Université de Toulouse , Toulouse , France .
Nanotoxicology. 2015 May;9(4):433-41. doi: 10.3109/17435390.2014.940406. Epub 2014 Jul 22.
Dendrimers are nanosized hyperbranched polymers synthesized through an iterative step-by-step process; their size and structure are perfectly controlled, and they are widely used for biomedical purposes. Previously, we showed that a phosphorous-based dendrimer capped with anionic AzaBisPhosphonate groups (so-called ABP dendrimer) has immunomodulatory and anti-inflammatory properties toward the human immune system. It dramatically inhibits the onset and development of experimental arthritis in a mouse model relevant for human rheumatoid arthritis, a chronic inflammatory disease of auto-immune origin. In this article, we demonstrate in an unprecedented study that cynomolgus macaques repeatedly injected with the ABP dendrimer displayed no adverse response. Indeed, biochemical, haematological, clotting and immunological parameters remained with a normal physiological range during the study. Moreover, quantification of serum cytokines and histopathological analyses failed to reveal any noticeable lesion or noteworthy non-physiological occurrence. These results strengthen the potential of the ABP dendrimer as an innovative drug-candidate for the treatment of inflammatory diseases and favor the regulatory preclinical development of the molecule.
树突状聚合物是通过迭代逐步合成的纳米超支化聚合物;其大小和结构可精确控制,广泛应用于生物医学领域。此前,我们表明,一种带有阴离子 AzaBisPhosphonate 基团封端的磷基树突状聚合物(所谓的 ABP 树突状聚合物)对人类免疫系统具有免疫调节和抗炎特性。它可显著抑制与人类类风湿关节炎相关的实验性关节炎在小鼠模型中的发生和发展,类风湿关节炎是一种自身免疫性的慢性炎症性疾病。在本文中,我们在一项前所未有的研究中证明,反复注射 ABP 树突状聚合物的食蟹猴没有出现不良反应。实际上,在研究过程中,生化、血液学、凝血和免疫学参数仍保持在正常生理范围内。此外,血清细胞因子的定量和组织病理学分析均未发现任何明显的病变或值得注意的非生理现象。这些结果增强了 ABP 树突状聚合物作为治疗炎症性疾病的创新药物候选物的潜力,并有利于该分子的监管临床前开发。