Characterisation of novel porphyrin-antibody conjugates for use in photoimmunotherapy of cancer (CROSBI ID 534473)
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Podaci o odgovornosti
Smith, Karen A. ; Pesa, Nela ; Staneloudi, Chrysovalanto ; Swann, Joanne ; Hudson, Robert ; Savoie, Huguette ; Boyle, Ross W. ; Greenman, John
engleski
Characterisation of novel porphyrin-antibody conjugates for use in photoimmunotherapy of cancer
Photodynamic therapy has become a useful tool in oncology but is often limited by side-effects caused by a lack of targeting of the photosensitiser. This problem can be circumvented by the conjugation of photosensitisers, such as porphyrins, to tumour-specific monoclonal antibodies (mAb). We have developed a simple method for the conjugation of porphyrin isothiocyanate molecules to proteins via the lysine residues. Here a panel of novel porphyrin isothiocyanate molecules were conjugated to a selection of mAb to allow targeted delivery of photosensitiser to tumour cells. Successful conjugation was verified by polyacrylamide gel electrophoresis, which also confirmed no disruption of the antibody after conjugation. Flow cytometry confirmed that there was no change in antibody binding or specificity caused by the conjugation procedure. Cytotoxicity was assesed by MMT assay after incubation of immunoconjugates with carcinoma cell lines and irradiation with non-thermal red light (>600 nm). The porphyrin LD50 concentrations showed that the antibody conjugates were more significantly effective at killing than the drug alone. Further investigation into the mode of cell death revealed that cell death resulted from the rapid onset of apoptosis after irradiation. In addition, confocal microscopy was used to visualise the localisation of the conjugates within the cell. It was shown that porphyrins can be conjugated to antibodies using a simple, widely applicable method that does not affect antibody binding. The lower LD50 concentrations of the bioconjugates, together with minimal non-specific bidning, means that these novel PDT reagents have potential as anti-tumour drugs.
Photodynamic therapy; Porphyrin; Monoclonal antibodies; Bioconjugation
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Podaci o prilogu
3637-3638.
2004.
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objavljeno
Podaci o matičnoj publikaciji
Anticancer Research
Delinassios, John G.
Atena: Int. Inst. Anticancer research
0250-7005
Podaci o skupu
7th International Conference of Anticancer Research
predavanje
25.10.2004-30.10.2004
Krf, Grčka
Povezanost rada
Kemija, Temeljne medicinske znanosti, Biologija