ENT Department, Section of Experimental Oncology and Nanomedicine (SEON), Else Kröner-Fresenius-Stiftung Professorship, Universitätsklinikum Erlangen, Erlangen, Germany.
Nanomedicine Research and Education Center, Institute of Pathophysiology, Semmelweis University, Budapest, Hungary.
Int J Nanomedicine. 2018 Mar 28;13:1899-1915. doi: 10.2147/IJN.S156528. eCollection 2018.
Rising criticism of currently available contrast agents for magnetic resonance imaging, either due to their side effects or limited possibilities in terms of functional imaging, evoked the need for safer and more versatile agents. We previously demonstrated the suitability of novel dextran-coated superparamagnetic iron oxide nanoparticles (SPION) for biomedical applications in terms of safety and biocompatibility.
In the present study, we investigated the size-dependent cross-linking process of these particles as well as the size dependency of their imaging properties. For the latter purpose, we adopted a simple and easy-to-perform experiment to estimate the relaxivity of the particles. Furthermore, we performed an extensive analysis of the particles' storage stability under different temperature conditions, showing their superb stability and the lack of any signs of agglomeration or sedimentation during a 12 week period.
Independent of their size, SPION displayed no irritation potential in a chick chorioallantoic membrane assay. Cell uptake studies of ultra-small (30 nm) SPION confirmed their internalization by macrophages, but not by non-phagocytic cells. Additionally, complement activation-related pseudoallergy (CARPA) experiments in pigs treated with ultra-small SPION indicated the absence of hypersensitivity reactions.
These results emphasize the exceptional safety of SPION, setting them apart from the existing SPION-based contrast agents and making them a very promising candidate for further clinical development.
由于目前用于磁共振成像的对比剂存在副作用或在功能成像方面的局限性，越来越多的人开始对其提出批评，这促使人们需要寻找更安全、更通用的对比剂。我们之前已经证明了新型葡聚糖包覆的超顺磁性氧化铁纳米粒子（SPION）在生物医学应用方面的安全性和生物相容性。
在本研究中，我们研究了这些粒子的尺寸依赖性交联过程以及其成像性能的尺寸依赖性。为了实现后者，我们采用了一种简单易行的实验来估计粒子的弛豫率。此外，我们还对粒子在不同温度条件下的储存稳定性进行了广泛的分析，结果表明这些粒子具有极好的稳定性，在 12 周的时间内没有任何聚集或沉淀的迹象。
无论其尺寸大小如何，SPION 在鸡胚绒毛尿囊膜试验中均未显示出任何刺激性。超小（30nm）SPION 的细胞摄取研究证实了巨噬细胞对其的内化，但非吞噬细胞则不能。此外，在接受超小 SPION 治疗的猪的补体激活相关假性过敏（CARPA）实验中，未发现过敏反应。
这些结果强调了 SPION 的卓越安全性，使其与现有的基于 SPION 的对比剂区别开来，使其成为进一步临床开发的极具潜力的候选者。
