DESIGN AND CYTOTOXICITY ASSESSMENT OF FULLERENOL DERIVATIVES AS NEUROIMAGING PARTICLES AND CARRIER MOLECULES ACROSS THE BBB

Date

2026-1-19

Author

Nursoy, Ahmet Zübeyir

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After its discovery, fullerene became a point of interest in the scientific community. Its insolubility in water initially prevented its use in biomedical applications. Fortunately, studies revealed that surface modifications, such as hydroxylation (converting fullerenes into fullerenols), can help tackle this problem. Activation with <i>p</i>-nitrophenyl chloroformate enables covalent binding of molecules with free amino groups to fullerenols, thereby expanding their utility in biochemical applications. A molecule was designed to mimic the properties of the HIV-1 Tat protein (TAT), a lysine (K)- and arginine (R)-rich cell-penetrating peptide (CPP). Levodopa was incorporated for its antioxidant and neuroprotective properties, as well as its hypothesized ability to hinder amyloid-beta (Aβ) π–π stacking a critical step in amyloid fibrillization. These tailored modifications yielded a fullerenol-based nanoparticle with enhanced blood-brain barrier (BBB) penetration, functioning as a nanocarrier. At effective concentrations, designed molecules exhibited negligible cytotoxicity in cell line models and conferred cellular protection against oxidative stress induced by lead (II) acetate and Aβ_1–42. One derivative demonstrated dual functionality: it interfered with Aβ fibrillation, suggesting potential as a non-invasive amyloidosis tracking agent (a hallmark of Alzheimer's Disease, AD), and it underwent conversion to neuromelanin <i>in vitro</i>, enabling MRI-based detection. This model molecule highlights the promise of multifunctional fullerenol-based systems as drug carriers, combining BBB penetrance, neuroprotection, and diagnostic capabilities.

Subject Keywords

Fullerenol, Neuroprotection, Nanocarrier, Cytotoxicity, Multifunctional nanoparticles

URI

https://hdl.handle.net/11511/118361

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Graduate School of Natural and Applied Sciences, Thesis