KLVFF-PEG- tailored Cyclodextrin Nanomagnets as Novel Tools for beta-Amyloide Targeting

Magnetic nanoparticles (MNPs) are largely utilized in magnetic-field-assisted bio-separation, bio- interaction, imaging and drug delivery, due to their large surface area and easy manipulation by an external magnetic force. Nanomagnets constituted magnetite functionalized with polymers, dendrimers and cyclodextrins functionalizing magnetite have been widely developed for therapy and diagnosis.1-2 Amphiphilic cyclodextrins (aCD) are largely engaged to therapeutic and diagnostic molecules.3-4 Here we propose novel nanomagnets (NMs) based on amphiphilic cyclodextrin heptakis (2-oligo(ethyleneoxide)-6-hexadecylthio-)-β-CD (SC16OH) -capping Fe3O4 NPs and tailored with Adamantanil-(PEG)4-KLVFF, (Ada-Pep), as nanoconstructs based on the self-recognizing sequence of the Amyloid-β (Aβ) peptides. Fe3O4@SC16OH NMs were prepared by mixing Fe3O4 NPs with an aqueous dispersion of SC16OH and then isolated by settling down with a magnet. Fe3O4@SC16OH/Ada-Pep NMs were obtained by hydration of an organic film of Ada-Pep, and isolated by centrifugation. In order to assess the recognition properties of the KLVFF active peptide, a magnetic cyclodextrin decorated with the scrambled units adamantanil-(PEG)4VFLKF (Ada-PepSCR) was fabricated. Peptidetailored NMs were characterized at solid state by TGA, STEM, AFM X-Ray Diffraction, XPS and magnetization mass measurements. In aqueous physiological solutions, DLS and Z-potential measurements point out a size of  200 nm and a negative surface potential ( -30 mV), dependently by the co-presence of aCD olygoethylenglycol chains and peptide units on the external fringe. The ability of nanomagnets to target the Aβ peptides was preliminarily studied in Aβ containing aqueous samples by means of MALDI-TOF MS. Our results indicate that the nanomagnets perform an unbiased Aβ-targeted fishing, suggesting their potential use as efficient diagnostic agents.