title: Water-Soluble Fullerene Derivatives as Brain Medicine: Surface Chemistry Determines If They Are Neuroprotective and Antitumor.
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 C60fullerene 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 C60with NSCs and glioma cells, producing either a neuroprotective or antitumor effect for possible treatment of CNS-related diseases.
authors.forename: Fu-Yu
authors.initials: FY
authors.lastname: Hsieh
authors.affiliation: Institute for Problems of Chemical Physics of Russian Academy of Sciences , Semenov Prospect 1, Chernogolovka 142432, Russian Federation.
authors.forename: A V
authors.initials: AV
authors.lastname: Zhilenkov
authors.affiliation: Institute for Problems of Chemical Physics of Russian Academy of Sciences , Semenov Prospect 1, Chernogolovka 142432, Russian Federation.
authors.forename: I I
authors.initials: II
authors.lastname: Voronov
authors.affiliation: Institute for Problems of Chemical Physics of Russian Academy of Sciences , Semenov Prospect 1, Chernogolovka 142432, Russian Federation.
authors.forename: E A
authors.initials: EA
authors.lastname: Khakina
authors.affiliation: Institute for Problems of Chemical Physics of Russian Academy of Sciences , Semenov Prospect 1, Chernogolovka 142432, Russian Federation.
authors.forename: D V
authors.initials: DV
authors.lastname: Mischenko
authors.affiliation: Institute for Problems of Chemical Physics of Russian Academy of Sciences , Semenov Prospect 1, Chernogolovka 142432, Russian Federation.|Skolkovo Institute of Science and Technology , Moscow 143005, Russian Federation.
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Troshin
authors.affiliation: Institute of Cellular and System Medicine, National Health Research Institutes , Zhunan 35053, Taiwan, R.O.C.
authors.forename: Shan-Hui
authors.identifier: http://orcid.org/0000-0002-3420-7662
authors.initials: SH
authors.lastname: Hsu
mesh_terms: D001812:Blood-Brain Barrier; D037741:Fullerenes / Q000737:chemistry*; D053758:Nanoparticles; D012995:Solubility; D013499:Surface Properties; D014867:Water
chemical_list: D037741:Fullerenes; D014867:Water
keywords: antitumor; glioblastoma; neural repair; surface functionalization; water-soluble C60 fullerene derivatives