Preparation of hybrid SPIONs and nanodiamonds in view of neurodegenerative diseases treatments

Superparamagnetic iron oxide nanoparticles (SPIONs) are widely used in biomedical applications due to their unique magnetic and physicochemical properties. Surface stabilization and functionalization further expand their applicability in biological environments and help overcome the challenges of achieving targeted therapy. Here, nanodiamonds (NDs) decorated with SPIONs were developed for a dual therapy approach combining magnetic and optical properties: NDs offer excellent properties for optical imaging while SPIONs serve as effective contrast agents. In the present study, amino-PEGylated SPIONs were covalently linked to carboxylated NDs via carbodiimide conjugation, to enhance the colloidal stability of the nanoparticles (NPs) and improve their biocompatibility and stealth properties. The functionalization process was evaluated using various analytical techniques, including TGA, XPS, FTIR, DLS, and zeta potential measurements, which confirmed and validated successful functionalization in each consecutive step. Given that organelle dysfunction plays a critical role in neurodegeneration, and in an effort to specifically target peroxisomes, the serine-lysine-leucine (SKL) peptide was thus anchored on ND-PEG-SPIONs surface with the remaining free amines. To further assess the biological response of these nanohybrids, their colloidal stability was compared in different biological media. Strikingly, based on the in vitro data obtained from BV-2 cells, we demonstrate that the nanoparticles accumulate intracellularly without inducing cell death or mitochondrial dysfunction, a result that fulfills a crucial prerequisite for their future application in targeted therapeutic delivery of antioxidant molecules to peroxisomes. This work thus paves the way for the development of in pexotherapy, opening new avenues for the treatment of neurodegenerative diseases associated with peroxisomal dysfunction.