NanoBBB · Transport of Engineered Nanomaterials across the blood-brain-barrier

Transport of Engineered Nanomaterials across the blood-brain-barrier

Over the last two decades, engineered nanomaterials (ENMs) have been used increasingly in novel technological, biomedical and consumer product applications. However, along with their ground-breaking potential, the unique properties of ENMs have also raised concerns about the potential for unintended consequences on environmental safety and human health. To date, potential toxicity mechanisms of ENMs are not well understood, and there are particular concerns for the potential of ENMs to elicit neurotoxicity. A possible mechanism for such an effect may be the result of ENMs crossing the blood brain barrier (BBB) and then directly or indirectly acting on the central nervous system (CNS). Currently, two key questions remain unanswered regarding the neurotoxicity of ENMs: (1) Can ENMs cross the BBB? Several in vitro and in vivo studies have suggested at least some ENMs can move across the BBB; the range of ENMs capable of such activity and the specific conditions required are still poorly understood, although it is recognised that the capacity of ENMs to cross the BBB is highly related to their physicochemical properties. The literature to date remains fragmented and inconsistent, while ENMs in many studies are not well characterized, making comparisons across the literature highly unreliable. A systematic investigation on the BBB-penetrating ability and its association with the intrinsic properties of ENMs is urgently needed. (2) What is the fate of ENMs within and beyond the BBB? i.e. the deposition, translocation, and transformation of ENMs during and after crossing the BBB. To date, this question has not been addressed well, primarily due to the difficulties in identification and localisation of ENMs in the complex brain environment - even more so for ENMs with high elemental backgrounds (e.g., C-based and Fe-based ENMs). Thus, novel approaches are urgently needed to enable a breakthrough in our understanding of ENM ability to cross the BBB and trace their path beyond. Project NanoBBB proposed combining novel labelling techniques with advanced in vitro methods coupled with in vivo experiments, enabling a uniquely new and systematic approach to elucidate the behaviour and fate of ENMs in the brain and contribute to their future safer design by avoiding any characteristics that may facilitate crossing the BBB.

Data: CORDIS, © European Union