Posted by 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.
It was demonstrated that CD-appended SPIONs, CySPIONs, provide a controlled way of simultaneously incorporating multiple functions that could benefit a drug delivery system targeting NPC or other diseases related to cholesterol imbalances in the brain. The multifunctional nanoparticles show negligible cytotoxicity. They are strongly endocytosed and localized in the lysosome of cells, where the pH-sensitive linker releases the appended CD. At least a similar amount of cholesterol is mobilized and exported outside the cells, as for monomeric CD. There is the potential for further improvement by tailoring its longer retention time, slower uptake and release than ethyl diamino CD. The significantly higher rate of transport of CySPION than free polymer through a model BBB could indicate a decisive advantage of the responsive, nanoparticle-based delivery system. Hence, this nanosystem demonstrates excellent potential as a therapeutic system for cholesterol-impaired diseases, deserving further investigation. Such continued in vivo studies will be facilitated by the built-in dual imaging modalities of fluorescence and magnetic resonance contrast.
Puglisi, A.; Bognanni, N.; Vecchio, G.; Bayir, E.; van Oostrum, P.; Shepherd, D.; Platt, F.; Reimhult, E. Grafting of Cyclodextrin to Theranostic Nanoparticles Improves Blood-Brain Barrier Model Crossing. Biomolecules 2023, 13, 573. https://doi.org/10.3390/biom13030573