Grafting of Cyclodextrin to Theranostic Nanoparticles Improves Blood-Brain Barrier Model Crossing
Antonino Puglisi,
Noemi Bognanni,
Graziella Vecchio,
Ece Bayir,
Peter van Oostrum,
Dawn Shepherd,
Frances Platt,
Erik Reimhult
Affiliations
Antonino Puglisi
Department of Bionanosciences, Institute of Biologically Inspired Materials, University of Natural Resources and Life Sciences (BOKU), 1190 Vienna, Austria
Noemi Bognanni
Department of Bionanosciences, Institute of Biologically Inspired Materials, University of Natural Resources and Life Sciences (BOKU), 1190 Vienna, Austria
Graziella Vecchio
Dipartimento di Scienze Chimiche, Università degli Studi di Catania, 95125 Catania, Italy
Ece Bayir
Central Research Testing and Analysis Laboratory Research and Application Center, Ege University Bornova, Izmir 35100, Turkey
Peter van Oostrum
Department of Bionanosciences, Institute of Biologically Inspired Materials, University of Natural Resources and Life Sciences (BOKU), 1190 Vienna, Austria
Dawn Shepherd
Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK
Frances Platt
Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK
Erik Reimhult
Department of Bionanosciences, Institute of Biologically Inspired Materials, University of Natural Resources and Life Sciences (BOKU), 1190 Vienna, Austria
Core–shell superparamagnetic iron oxide nanoparticles hold great promise as a theranostic platform in biological systems. Herein, we report the biological effect of multifunctional cyclodextrin-appended SPIONs (CySPION) in mutant Npc1-deficient CHO cells compared to their wild type counterparts. CySPIONs show negligible cytotoxicity while they are strongly endocytosed and localized in the lysosomal compartment. Through their bespoke pH-sensitive chemistry, these nanoparticles release appended monomeric cyclodextrins to mobilize over-accumulated cholesterol and eject it outside the cells. CySPIONs show a high rate of transport across blood–brain barrier models, indicating their promise as a therapeutic approach for cholesterol-impaired diseases affecting the brain.
