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Disorders and diseases of the brain present an enormous challenge due to the physical and physiological properties of the blood-brain barrier (BBB), making entry for therapeutics difficult. In recent years, increased research has focused on using magnetic ferrite nanoparticles (NPs) in various biomedical applications. In this study, we report on the design of ferrite NPs for traversing the BBB. Core ferrite CoFe2O4 and Mg0.5Co0.5Fe2O4 NPs were synthesized using the glycol-thermal route and coated with chitosan (CS). A BBB-targeting peptide, Angiopep-2 (ANG), was covalently conjugated to the coated NPs. The physical, chemical, and magnetic properties of the core and derivative ferrite NPs were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), high-resolution transmission electron microscopy (HR-TEM), nanoparticle tracking analysis (NTA) and vibrating sample magnetometer (VSM). Docking studies were conducted using Autodock Vina software for binding. XRD, HR-TEM and VSM results revealed spinel crystalline ferrite core NPs exhibiting superparamagnetic behaviour. Particle core sizes of the ferrite NPs were below 13.6 nm. The FTIR spectra showed characteristic peak shifts upon CS-coating and conjugation with Angiopep-2, thus confirming functionalization. Hydrodynamic sizes of 90.4 nm and 152. nm were reported for the ANG-CS-CoFe2O4, and ANG-CS-Mg0.5Co0.5Fe2O4, respectively. ANG-CS-Mg0.5Co0.5Fe2O4 presented the most stability with a zeta potential (+29.0 mV), while ANG-CS-CoFe2O4 has +19.2 mV. Molecular docking investigations revealed binding energies for the CS-conjugated ANG of -5.67 kCal/mol, suggesting that the LRP-1 receptor was not significantly hindered. These NPs exhibit potential for targeted CNS delivery and can be explored for in vitro gene and drug delivery.
Keywords: Ferrites, magnetic nanoparticles, Angiopep, blood-brain barrier, docking, LRP-1 receptor© This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.