Graphene quantum dots: From efficient preparation to safe renal excretion
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f Excellence for Nanostructured Materials (CENMAT), INSTM, Department of Chemical and Pharmaceutical Sciences, University of Trieste, Via L. Giorgieri 1, 34127 Trieste, Italy 2 Current address: Laboratoire LG2A – CNRS UMR 7378, Université de Picardie Jules Verne, 33 rue Saint Leu - UFR des Sciences, 80039 Amiens, France 3 Instituto de Carboquímica (CSIC), C/Miguel Luesma Castán 4, E-50018 Zaragoza, Spain 4 Renal Research Laboratory-Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via Pace 9, 20122 Milan, Italy 5 Dipartimento di Chimica, Materiali ed Ingegneria Chimica “G. Natta”, Politecnico di Milano, Via Mancinelli 7, 20131 Milan, Italy 6 Unit of Nephrology, Dialysis and Renal Transplant Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, via della commenda 4, 20122 Milan, Italy 7 Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy 8 Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC and the Barcelona Institute of Science and Technology, Campus UAB, Bellaterra, 08193 Barcelona, Spain § Caroline Hadad and José Miguel González-Domínguez contributed equally to this work. ¶ Silvia Armelloni and Deborah Mattinzoli contributed equally to this work. © The Author(s) 2020 Received: 23 June 2020 / Revised: 3 September 2020 / Accepted: 6 September 2020
ABSTRACT Carbon nanomaterials offer excellent prospects as therapeutic agents, and among them, graphene quantum dots (GQDs) have gained considerable interest thanks to their aqueous solubility and intrinsic fluorescence, which enable their possible use in theranostic approaches, if their biocompatibility and favorable pharmacokinetic are confirmed. We prepared ultra-small GQDs using an alternative, reproducible, top-down synthesis starting from graphene oxide with a nearly 100% conversion. The materials were tested to assess their safety, demonstrating good biocompatibility and ability in passing the ultrafiltration barrier using an in vitro model. This leads to renal excretion without affecting the kidneys. Moreover, we studied the GQDs in vivo biodistribution confirming their efficient renal clearance, and we demonstrated that the internalization mechanism into podocytes is caveolae-mediated. Therefore, considering the reported characteristics, it appears possible to vehiculate compounds to kidneys by means of GQDs, overcoming problems related to lysosomal degradation.
KEYWORDS graphene quantum dots, podocytes, biodistribution, uptake pathway, renal clearance, nanocarrier
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Introduction
Since 2004, the landmark study by Geim and Novoselov drew the attention into graphene, that presents undisputed potential in many areas, particularly in optoelectronics, due to its unique electronic structure and overall physical properties [1]. Its oxidized derivative, graphene oxide (GO) is also largely popular for its high hydrophilicity, easy handling and affordable production. Also in this case there is an interesting niche of applications, as electrochemistry [2] and biotechnology [3] and from the thorough stud
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