Synthesis and Characterization of p-Borono-Phenylalanine-Branched Polypeptide-Monoclonal Antibody Ternary Systems for Potential Use in Boron Neutron Capture Therapy (BNCT)
| Autor: | Zsuzsa Nagy, J. A. Clegg, János Gergely, Gábor Mezö, Judit Kajtár, Mária Szekerke, Gabriella Sármay, Ferenc Hudecz |
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| Rok vydání: | 1996 |
| Předmět: |
Polymers and Plastics
Stereochemistry medicine.drug_class medicine.medical_treatment 0206 medical engineering chemistry.chemical_element Bioengineering Phenylalanine 02 engineering and technology Monoclonal antibody Biomaterials chemistry.chemical_compound Antigen Materials Chemistry medicine Boron Melanoma 021001 nanoscience & nanotechnology medicine.disease 020601 biomedical engineering Combinatorial chemistry Radiation therapy chemistry Polylysine 0210 nano-technology Conjugate |
| Zdroj: | Journal of Bioactive and Compatible Polymers. 11:263-285 |
| ISSN: | 1530-8030 0883-9115 |
| Popis: | The application of the 10B ( n,α) 7Li capture reaction to cancer radiotherapy (Boron Neutron Capture Therapy) was studied to avoid the inherent disadvantages of conventional radiation therapy. p-Borono-phenylalanine (Bph) was used as the 10B source and mAb produced against HCMB melanoma cells was applied as targeting device. Since extensive direct boronation of mAb led diminished recognition of antigens, an intermediate carrier was used. Nontoxic, biocompatible, biodegradable and weakly immunogenic branched polypeptides with a polylysine backbone was used to carry a high number of 10B. Protected 10B-Bph was coupled by four different methods to polycationic branched polypeptides. The coupling efficiency varied according to the experimental conditions, with a maximum of 90%. The chiroptical properties of the conjugates indicated an ordered conformation which increased with the number of coupled Bph. The whole body survival (WBS) and tissue distribution profile of mAb (8/6 IgG2a) were markedly altered after conjugation with Bph-branched polypeptide. Decreased WBS and intermediate-carrier-dependent accumulation in the spleen, liver and kidney was observed 24 h after iv. administration. After joining only a few chains of the highly loaded Bph-AK conjugate to mAb, the binding activity of the mAb in the ternary system was preserved compared to control. |
| Databáze: | OpenAIRE |
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