Generalized arterial calcification of infancy (GACI) and pseudoxanthoma elasticum (PXE) are characterized by pathologic calcifications in the media of large- and medium sized arteries. GACI is associated with biallelic mutations in ENPP1 in the majority of cases, whereas mutations in ABCC6 are known to cause PXE. Different treatment approaches including bisphosphonates and orally administered pyrophosphate (PP_i) were investigated in recent years, but reversion of calcification could not be achieved. With this study, we pursued the idea of a combination of controlled drug delivery through nanoparticles and active targeting via antibody conjugation to develop a treatment for GACI and PXE.

To establish a suitable drug delivery system, the chelating drug diethylenetriamine pentaacetic acid (DTPA) was conjugated to nanoparticles composed of human serum albumin (HSA) as biodegradable and non-toxic particle matrix. To accomplish an active targeting of the elastic fibers exposed through calcification of the affected areas, the nanoparticle surface was functionalized with an anti-elastin antibody. Cytotoxicity and cell interaction studies revealed favorable preconditions for the intended i.v. application. The chelating ability was evaluated in vitro and ex vivo on aortic ring culture isolated from two mouse models of GACI and PXE. The positive results led to the conclusion that the produced nanoparticles might be a promising therapy in the treatment of GACI and PXE.

婴儿的广义动脉钙化（GACI）和弹性假黄瘤（PXE）的特征是大中型动脉介质中的病理性钙化。在大多数情况下，GACI与ENPP1中的双等位基因突变相关，而已知ABCC6中的突变会引起PXE。近年来，已研究了包括双膦酸盐和口服焦磷酸盐（PP _i）在内的不同治疗方法，但无法实现钙化的逆转。通过这项研究，我们追求了通过纳米颗粒控制药物递送和通过抗体偶联进行主动靶向相结合的思想，从而开发出针对GACI和PXE的治疗方法。

为了建立合适的药物递送系统，将螯合剂二亚乙基三胺五乙酸（DTPA）与作为可生物降解且无毒的颗粒基质的人血清白蛋白（HSA）组成的纳米颗粒偶联。为了实现对受影响区域钙化暴露的弹性纤维的主动靶向，用抗弹性蛋白抗体对纳米颗粒表面进行了功能化。细胞毒性和细胞相互作用研究揭示了预期的静脉应用的有利前提。螯合能力在体外和离体评估从两个GACI和PXE小鼠模型分离的主动脉环培养物中。积极的结果得出结论，即所产生的纳米颗粒可能是治疗GACI和PXE的有前途的疗法。