Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture Therapy
Carboranes are promising agents for applications in boron neutron capture therapy (BNCT), but their hydrophobicity prevents their use in physiological environments. Here, by using reverse docking and molecular dynamics (MD) simulations, we identified blood transport proteins as candidate carriers of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/13/11/1770 |
| _version_ | 1797597004478545920 |
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| author | Tainah Dorina Marforio Edoardo Jun Mattioli Francesco Zerbetto Matteo Calvaresi |
| author_facet | Tainah Dorina Marforio Edoardo Jun Mattioli Francesco Zerbetto Matteo Calvaresi |
| author_sort | Tainah Dorina Marforio |
| collection | DOAJ |
| description | Carboranes are promising agents for applications in boron neutron capture therapy (BNCT), but their hydrophobicity prevents their use in physiological environments. Here, by using reverse docking and molecular dynamics (MD) simulations, we identified blood transport proteins as candidate carriers of carboranes. Hemoglobin showed a higher binding affinity for carboranes than transthyretin and human serum albumin (HSA), which are well-known carborane-binding proteins. Myoglobin, ceruloplasmin, sex hormone-binding protein, lactoferrin, plasma retinol-binding protein, thyroxine-binding globulin, corticosteroid-binding globulin and afamin have a binding affinity comparable to transthyretin/HSA. The carborane@protein complexes are stable in water and characterized by favorable binding energy. The driving force in the carborane binding is represented by the formation of hydrophobic interactions with aliphatic amino acids and BH-π and <i>C</i>H-π interactions with aromatic amino acids. Dihydrogen bonds, classical hydrogen bonds and surfactant-like interactions also assist the binding. These results (i) identify the plasma proteins responsible for binding carborane upon their intravenous administration, and (ii) suggest an innovative formulation for carboranes based on the formation of a carborane@protein complex prior to the administration. |
| first_indexed | 2024-03-11T03:00:41Z |
| format | Article |
| id | doaj.art-6ce736bfdb604c298a541bcd55c07fba |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-11T03:00:41Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-6ce736bfdb604c298a541bcd55c07fba2023-11-18T08:19:17ZengMDPI AGNanomaterials2079-49912023-05-011311177010.3390/nano13111770Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture TherapyTainah Dorina Marforio0Edoardo Jun Mattioli1Francesco Zerbetto2Matteo Calvaresi3Dipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum-Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, ItalyDipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum-Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, ItalyDipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum-Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, ItalyDipartimento di Chimica “Giacomo Ciamician”, Alma Mater Studiorum-Università di Bologna, Via Francesco Selmi 2, 40126 Bologna, ItalyCarboranes are promising agents for applications in boron neutron capture therapy (BNCT), but their hydrophobicity prevents their use in physiological environments. Here, by using reverse docking and molecular dynamics (MD) simulations, we identified blood transport proteins as candidate carriers of carboranes. Hemoglobin showed a higher binding affinity for carboranes than transthyretin and human serum albumin (HSA), which are well-known carborane-binding proteins. Myoglobin, ceruloplasmin, sex hormone-binding protein, lactoferrin, plasma retinol-binding protein, thyroxine-binding globulin, corticosteroid-binding globulin and afamin have a binding affinity comparable to transthyretin/HSA. The carborane@protein complexes are stable in water and characterized by favorable binding energy. The driving force in the carborane binding is represented by the formation of hydrophobic interactions with aliphatic amino acids and BH-π and <i>C</i>H-π interactions with aromatic amino acids. Dihydrogen bonds, classical hydrogen bonds and surfactant-like interactions also assist the binding. These results (i) identify the plasma proteins responsible for binding carborane upon their intravenous administration, and (ii) suggest an innovative formulation for carboranes based on the formation of a carborane@protein complex prior to the administration.https://www.mdpi.com/2079-4991/13/11/1770carboraneboron neutron capture therapy (BNCT)virtual screeningdockingreverse dockingMD simulations |
| spellingShingle | Tainah Dorina Marforio Edoardo Jun Mattioli Francesco Zerbetto Matteo Calvaresi Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture Therapy Nanomaterials carborane boron neutron capture therapy (BNCT) virtual screening docking reverse docking MD simulations |
| title | Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture Therapy |
| title_full | Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture Therapy |
| title_fullStr | Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture Therapy |
| title_full_unstemmed | Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture Therapy |
| title_short | Exploiting Blood Transport Proteins as Carborane Supramolecular Vehicles for Boron Neutron Capture Therapy |
| title_sort | exploiting blood transport proteins as carborane supramolecular vehicles for boron neutron capture therapy |
| topic | carborane boron neutron capture therapy (BNCT) virtual screening docking reverse docking MD simulations |
| url | https://www.mdpi.com/2079-4991/13/11/1770 |
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