Abstract
Delivering drugs to the central nervous system (CNS) is a major challenge in treating CNS-related diseases. Nanoparticles that can cross blood-brain barrier (BBB) are potential tools. In this study, water-soluble C60 fullerene derivatives with different types of linkages between the fullerene cage and the solubilizing addend were synthesized (compounds 1-3: C-C bonds, compounds 4-5: C-S bonds, compound 6: C-P bonds, and compounds 7-9: C-N bonds). Fullerene derivatives 1-6 were observed to induce neural stem cell (NSC) proliferation in vitro and rescue the function of injured CNS in zebrafish. Fullerene derivatives 7-9 were found to inhibit glioblastoma cell proliferation in vitro and reduce glioblastoma formation in zebrafish. These effects were correlated with the cell metabolic changes. Particularly, compound 3 bearing residues of phenylbutiryc acids significantly promoted NSC proliferation and neural repair without causing tumor growth. Meanwhile, compound 7 with phenylalanine appendages significantly inhibited glioblastoma growth without retarding the neural repair. We conclude that the surface functional group determines the properties as well as the interactions of C60 with NSCs and glioma cells, producing either a neuroprotective or antitumor effect for possible treatment of CNS-related diseases.
Published Version
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