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A Boron Delivery Antibody (BDA) with Boronated Specific Residues: New Perspectives in Boron Neutron Capture Therapy from an In Silico Investigation.

ABSTRACT: Boron Neutron Capture Therapy (BNCT) is a tumor cell-selective radiotherapy based on a nuclear reaction that occurs when the isotope boron-10 (¹⁰B) is radiated by low-energy thermal neutrons or epithermal neutrons, triggering a nuclear fission response and enabling a selective administration of irradiation to cells. Hence, we need to create novel delivery agents containing ¹⁰B with high tumor selectivity, but also exhibiting low intrinsic toxicity, fast clearance from normal tissue and blood, and no pharmaceutical effects. In the past, boronated monoclonal antibodies have been proposed using large boron-containing molecules or dendrimers, but with no investigations in relation to maintaining antibody specificity and structural and functional features. This work aims at improving the potential of monoclonal antibodies applied to BNCT therapy, identifying in silico the best native residues suitable to be substituted with a boronated one, carefully evaluating the effect of boronation on the 3D structure of the monoclonal antibody and on its binding affinity. A boronated monoclonal antibody was thus generated for specific ¹⁰B delivery. In this context, we have developed a case study of Boron Delivery Antibody Identification Pipeline, which has been tested on cetuximab. Cetuximab is an epidermal growth factor receptor (EGFR) inhibitor used in the treatment of metastatic colorectal cancer, metastatic non-small cell lung cancer, and head and neck cancer.

SUBMITTER: Rondina A

PROVIDER: S-EPMC8618907 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Thermal Sensitive Liposomes Improve Delivery of Boronated Agents for Boron Neutron Capture Therapy.

Project description:PURPOSE:Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation requires sufficient tumor boron delivery while minimizing nonspecific accumulation. METHODS:Thermal sensitive liposomes (TSLs) were designed to have a stable drug payload at physiological temperatures but engineered to have high permeability under mild hyperthermia. RESULTS:We found that TSLs improved the tumor-specific delivery of boronophenylalanine (BPA) and boronated 2-nitroimidazole derivative B-381 in D54 glioma cells. Uniquely, the 2-nitroimidazole moiety extended the tumor retention of boron content compared to BPA. CONCLUSION:This is the first study to show the delivery of boronated compounds using TSLs for BNCT, and these results will provide the basis of future clinical trials using TSLs for BNCT.

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A Boronated Derivative of Temozolomide Showing Enhanced Efficacy in Boron Neutron Capture Therapy of Glioblastoma.

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Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB0,+, LAT1 and LAT2.

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Amino Acid-Based Boron Carriers in Boron Neutron Capture Therapy (BNCT).

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Boron-peptide conjugates with angiopep-2 for boron neutron capture therapy.

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Project description:Boron neutron capture therapy (BNCT) is a re-emerging therapy with the ability to selectively kill tumor cells. After the boron delivery agents enter the tumor tissue and enrich the tumor cells, the thermal neutrons trigger the fission of the boron atoms, leading to the release of boron atoms and then leading to the release of the α particles (4He) and recoil lithium particles (7Li), along with the production of large amounts of energy in the narrow region. With the advantages of targeted therapy and low toxicity, BNCT has become a unique method in the field of radiotherapy. Since the beginning of the last century, BNCT has been emerging worldwide and gradually developed into a technology for the treatment of glioblastoma multiforme, head and neck cancer, malignant melanoma, and other cancers. At present, how to develop and innovate more efficient boron delivery agents and establish a more accurate boron-dose measurement system have become the problem faced by the development of BNCT. We discuss the use of boron delivery agents over the past several decades and the corresponding clinical trials and preclinical outcomes. Furthermore, the discussion brings recommendations on the future of boron delivery agents and this therapy.

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Nanostructured Boron Nitride With High Water Dispersibility For Boron Neutron Capture Therapy.

Project description:Highly water dispersible boron based compounds are innovative and advanced materials which can be used in Boron Neutron Capture Therapy for cancer treatment (BNCT). Present study deals with the synthesis of highly water dispersible nanostructured Boron Nitride (BN). Unique and relatively low temperature synthesis route is the soul of present study. The morphological examinations (Scanning/transmission electron microscopy) of synthesized nanostructures showed that they are in transient phase from two dimensional hexagonal sheets to nanotubes. It is also supported by dual energy band gap of these materials calculated from UV- visible spectrum of the material. The theoretically calculated band gap also supports the same (calculated by virtual nano lab Software). X-ray diffraction (XRD) analysis shows that the synthesized material has deformed structure which is further supported by Raman spectroscopy. The structural aspect of high water disperse ability of BN is also studied. The ultra-high disperse ability which is a result of structural deformation make these nanostructures very useful in BNCT. Cytotoxicity studies on various cell lines (Hela(cervical cancer), human embryonic kidney (HEK-293) and human breast adenocarcinoma (MCF-7)) show that the synthesized nanostructures can be used for BNCT.

| S-EPMC5069687 | biostudies-literature

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