ABSTRACT
Research into targeting of photodynamic sensitisers to specific biological tissue has been an area of increasing interest over the last twenty years. A significant number of these investigations have involved the use of antibodies or antibody fragments, and the field of photosensitiser bioconjugation is now an established area in its own right. This review seeks to bring together the diverse range of methodology now available for the efficient attachment of photodynamic agents to antibodies. The chemistry involved to obtain the complementary functionality required, on both photosensitiser and antibody, for successful conjugation is also discussed.
Subject(s)
Antibodies/chemistry , Photosensitizing Agents/chemistry , Acrylamides/chemistry , Carbodiimides/chemistry , Fullerenes/chemistry , Humans , Isothiocyanates/chemistry , Neoplasms/drug therapy , Photochemotherapy , Photosensitizing Agents/therapeutic use , Polyglutamic Acid/chemistry , Polyvinyl Alcohol/chemistryABSTRACT
Synthesis of three new cationic thiol-reactive maleimide-porphyrin derivatives and their use in site-specific conjugation to monoclonal antibodies is reported. The selective reactivity toward thiols is demonstrated using competition experiments, where both thiols and amines are present. This selectivity was used to successfully achieve specific conjugation of two porphyrins to cysteine residues present in the antiangiogenic antibody L19, expressed in small immunoprotein (SIP) format. The effect of length and hydrophilicity of the linkage between porphyrin and maleimide was also investigated, and maximum photocytotoxicity was achieved with the longest and most hydrophilic chain. Immunoreactivity and in vitro photocytotoxicity for these well-characterized porphyrin-antibody conjugates are described.
