title: Synthesis and in vitro testing of a pyropheophorbide-a-fullerene hexakis adduct immunoconjugate for photodynamic therapy.
abstract: The employment of carriers to enhance drug selectivity is one of the strategies to increase the efficacy and reduce the side effects of antitumor therapy. The concept of a modular carrier system (MCS) was developed to construct a complex drug having a high efficacy and selectivity. An MCS employs diverse units or modules: beside the therapeutic unit, an addressing unit (e.g., an antibody) serves to direct the drug to its target, and a multiplying unit has the role of increasing the number of biological active moieties the system can carry. In this paper, we report on the synthesis of a modular carrier system in which the role of multiplying unit is given to a [5:1]fullerene hexakis adduct. This fullerene hexaadduct has five malonate spacers which can bind two therapeutic units (the photosensitizer pyropheophorbide-a) each, for a total of ten, and a longer malonate spacer which serves for the conjugation to the addressing unit, the monoclonal antibody rituximab. Confocal microscopy studies using Epstein-Barr virus-transformed B-lymphocytes and Jurkat cells showed that the antibody conjugate conserves the affinity for its receptor (CD20) and its selectivity toward CD20 positive B-lymphocytes. On the contrary, the antibody-free complex did not show any bounding or intracellular uptake.
authors.affiliation: Universitätsklinikum Charité, Hautklinik, Photobiologisches Labor, Berlin, Germany. norbert.jux@chemie.uni-erlangen.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: Eugeny A
authors.initials: EA
authors.lastname: Ermilov
authors.forename: Norbert
authors.initials: N
authors.lastname: Jux
authors.forename: Beate
authors.initials: B
authors.lastname: Röder
authors.forename: Andreas
authors.initials: A
authors.lastname: Hirsch
authors.forename: Fritz
authors.initials: F
authors.lastname: Böhm
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002734:Chlorophyll / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers; D037741:Fullerenes / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry* / Q000494:pharmacology; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology; D000069283:Rituximab; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D004337:Drug Carriers; D037741:Fullerenes; D018796:Immunoconjugates; D017319:Photosensitizing Agents; D002734:Chlorophyll; C040298:pyropheophorbide a; D000069283:Rituximab