Updated project metadata. In this work, we performed an in vitro investigation of GRM interactions with the BBB. To this aim,we employed GRMs with different surface chemistry and stability, both murine and human models of increasing complexity, and a portfolio of complementary label-free analytical techniques. The use of label-free strategies allows to avoid the problem of fluorescent tag interference and leaching, which makes the results on the bionano-interactions difficult to interpret.42-43 The workflow developed in this paper is widely applicable to study the translocation of different micro- and nano-materials and represents a valuable method to reduce the more expensive and ethically concerning in vivo biodistribution studies.