Grafting of Cyclodextrin to Theranostic Nanoparticles Improves Blood-Brain Barrier Model Crossing.
Antonino PuglisiNoemi BognanniGraziella VecchioEce BayirPeter van OostrumDawn ShepherdFrances Mary PlattErik ReimhultPublished in: Biomolecules (2023)
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.
Keyphrases
- blood brain barrier
- wild type
- iron oxide nanoparticles
- induced apoptosis
- cerebral ischemia
- cell cycle arrest
- capillary electrophoresis
- endoplasmic reticulum stress
- drug delivery
- low density lipoprotein
- iron oxide
- oxidative stress
- fluorescence imaging
- white matter
- big data
- cell death
- multiple sclerosis
- cancer therapy
- breast reconstruction
- deep learning
- artificial intelligence