896 Photodynamic therapy of tumours: New advances

Abstract

Studies on transport of HpD by high and low density proteins (VLDL, IDL and HDL) have suggested that apparently lipoproteins possess two classes of binding sites for Hp which are probably located in the apoprotein matrix and the lipid core, respectively. Lipoproteins play an important role in the transport of haematoporphyrins (Hp and HpD) in the bloodstream, it has been suggested that tumor localising property of the porphyrin photosensitisers used in photodynamic therapy (PDT) is related to such binding, particularly to low lipoprotein. LDL binds to specific receptors on cellular membranes by arginy 1 and lysyl residues. Chemical modification of these residues abolishes the interaction between lipoproteins and receptors both in vitro and in vivo. In vitro studies have also demonstrated that tumors have a higher affinity binding for LDL because of an increase of the number of membrane LDL-receptors. To a greater understanding of transport mechanism of porphirins we have studied the affinity of HpD to proteic amino acid by thin layer chromatography and nuclear magnetic resonance (NMR), using a standard mixture. Our results indicate that the tryptophane is the aminoacid mainly involved in HpD binding. Whereas other aromatic aminoacids are at secondary levels. Furthermore a study on the binding sites of human serum albumin to HpD by NMR is also presented. A better knowledge of these binding sites will allow to improve photodynamic therapy and to transfer selectively antiblastic chemo therapic drugs in neoplastic cells. Studies on transport of HpD by high and low density proteins (VLDL, IDL and HDL) have suggested that apparently lipoproteins possess two classes of binding sites for Hp which are probably located in the apoprotein matrix and the lipid core, respectively. Lipoproteins play an important role in the transport of haematoporphyrins (Hp and HpD) in the bloodstream, it has been suggested that tumor localising property of the porphyrin photosensitisers used in photodynamic therapy (PDT) is related to such binding, particularly to low lipoprotein. LDL binds to specific receptors on cellular membranes by arginy 1 and lysyl residues. Chemical modification of these residues abolishes the interaction between lipoproteins and receptors both in vitro and in vivo. In vitro studies have also demonstrated that tumors have a higher affinity binding for LDL because of an increase of the number of membrane LDL-receptors. To a greater understanding of transport mechanism of porphirins we have studied the affinity of HpD to proteic amino acid by thin layer chromatography and nuclear magnetic resonance (NMR), using a standard mixture. Our results indicate that the tryptophane is the aminoacid mainly involved in HpD binding. Whereas other aromatic aminoacids are at secondary levels. Furthermore a study on the binding sites of human serum albumin to HpD by NMR is also presented. A better knowledge of these binding sites will allow to improve photodynamic therapy and to transfer selectively antiblastic chemo therapic drugs in neoplastic cells.