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

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• 作者：Fiorenza Rancan ; Matthias Helmreich ; Andreas Mö ; lich ; Eugeny A. Ermilov ; Norbert Jux ; Beate Rö ; der ; Andreas Hirsch ; Fritz Bö ; hm
• 刊名：Bioconjugate Chemistry
• 出版年：2007
• 出版时间：July 2007
• 年：2007
• 卷：18
• 期：4
• 页码：1078 - 1086
• 全文大小：637K
• 年卷期：v.18,no.4(July 2007)
• ISSN：1520-4812

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.