文摘
The employment of carriers to enhance drug selectivity is one of the strategies to increase the efficacy and reducethe side effects of antitumor therapy. The concept of a modular carrier system (MCS) was developed to constructa complex drug having a high efficacy and selectivity. An MCS employs diverse units or modules: beside thetherapeutic unit, an addressing unit (e.g., an antibody) serves to direct the drug to its target, and a multiplyingunit has the role of increasing the number of biological active moieties the system can carry. In this paper, wereport 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 therapeuticunits (the photosensitizer pyropheophorbide-a) each, for a total of ten, and a longer malonate spacer which servesfor the conjugation to the addressing unit, the monoclonal antibody rituximab. Confocal microscopy studies usingEpstein-Barr virus-transformed B-lymphocytes and Jurkat cells showed that the antibody conjugate conservesthe affinity for its receptor (CD20) and its selectivity toward CD20 positive B-lymphocytes. On the contrary, theantibody-free complex did not show any bounding or intracellular uptake.