title: Intracellular uptake and phototoxicity of 3(1),3(2)-didehydrophytochlorin-fullerene hexaadducts.
abstract: C(60)-fullerene derivatives are potential building blocks in modular carrier systems for selective tumor targeting. In [5:1] fullerene hexakis adducts, one position can be occupied by an addressing unit (e.g. monoclonal antibody) while the other five positions are suitable for dendrimers or spacers loaded with several drug moieties. This article reports intracellular uptake and phototoxicity of three fullerene hexakis adducts coupled with a different number of photosensitizers: a bis(3(1),3(2)-didehydrophytochlorin)-fullerene [5:1]-hexaadduct (FHP1), a fullerene [5:1]-hexaadduct with six 3(1),3(2)-didehydrophytochlorin groups (FHP6) and a fullerene [6:0]-hexaadduct that carries 12 3(1),3(2)-didehydrophytochlorin units (FHP12). The most promising complex, the hexa-3(1),3(2)-didehydrophytochlorin fullerene hexaadduct FHP6, was also compared with its fullerene-free analogous derivative P6. It was found that the extent of intracellular uptake is influenced by both nanomolecular size and asymmetry (amphiphilicity) of the fullerene complexes. The degree and mechanism of phototoxicity was found to depend on intracellular concentrations and singlet oxygen quantum yields.
authors.affiliation: Hautklinik, Photobiologisches Labor, Universitätsklinikum Charité, Berlin, Germany. fiorenza.rancan@charite.de
authors.forename: Fiorenza
authors.initials: F
authors.lastname: Rancan
authors.forename: Matthias
authors.initials: M
authors.lastname: Helmreich
authors.forename: Andreas
authors.initials: A
authors.lastname: Mölich
authors.forename: Norbert
authors.initials: N
authors.lastname: Jux
authors.forename: Andreas
authors.initials: A
authors.lastname: Hirsch
authors.forename: Beate
authors.initials: B
authors.lastname: Röder
authors.forename: Fritz
authors.initials: F
authors.lastname: Böhm
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D037741:Fullerenes / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D006801:Humans; D019169:Jurkat Cells; D010777:Photochemistry; D011166:Porphyrins / Q000737:chemistry*
chemical_list: C526323:3(1),3(2)-didehydrophytochlorin; D037741:Fullerenes; D011166:Porphyrins