Synthesis and in Vitro Testing of a Pyropheophorbide- alpha -Fullerene Hexakis Adduct Immunoconjugate for Photodynamic Therapy

• Published in: Bioconjugate chemistry Vol. 18; no. 4; pp. 1078 - 1086
• Main Authors: Rancan, F, Helmreich, M, Moelich, A, Ermilov, E A, Jux, N, Roeder, B, Hirsch, A, Boehm, F
• Format: Journal Article
• Language: English
• Published: 01.07.2007
• ISSN: 1043-1802
• DOI: 10.1021/bc0603337

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 drag 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- alpha ) 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.