Synthesis and characterization of p-borono-phenylalanine-branched polypeptide-monoclonal antibody ternary systems for potential use in boron neutron capture therapy (BNCT)

G. Mező, F. Hudecz, Mária Szekerke, Judit Kajtár, G. Sármay, J. Gergely, Zsuzsa Nagy

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7 Citations (Scopus)

Abstract

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 10-B-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.

Original languageEnglish
Pages (from-to)263-285
Number of pages23
JournalJournal of Bioactive and Compatible Polymers
Volume11
Issue number4
Publication statusPublished - Oct 1996

Fingerprint

Boron Neutron Capture Therapy
Boron
Monoclonal antibodies
Polypeptides
Ternary systems
Phenylalanine
Neutrons
Monoclonal Antibodies
Radiotherapy
Peptides
Antigens
Joining
Liver
Conformations
Polylysine
Tissue
Tissue Distribution
Melanoma
Spleen
Kidney

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Materials Chemistry
  • Polymers and Plastics

Cite this

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title = "Synthesis and characterization of p-borono-phenylalanine-branched polypeptide-monoclonal antibody ternary systems for potential use in boron neutron capture therapy (BNCT)",
abstract = "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 10-B-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.",
author = "G. Mező and F. Hudecz and M{\'a}ria Szekerke and Judit Kajt{\'a}r and G. S{\'a}rmay and J. Gergely and Zsuzsa Nagy",
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T1 - Synthesis and characterization of p-borono-phenylalanine-branched polypeptide-monoclonal antibody ternary systems for potential use in boron neutron capture therapy (BNCT)

AU - Mező, G.

AU - Hudecz, F.

AU - Szekerke, Mária

AU - Kajtár, Judit

AU - Sármay, G.

AU - Gergely, J.

AU - Nagy, Zsuzsa

PY - 1996/10

Y1 - 1996/10

N2 - 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 10-B-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.

AB - 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 10-B-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.

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