Targeting of Basophil and Mast Cell Pro-Allergic Reactivity Using Functionalised Gold Nanoparticles
Calcineurin inhibitors potentially prevent pro-allergic mediator release from basophils and mast cells but are rarely used systemically due to ubiquitous expressions of target signaling proteins. However, specific targeting of allergic effector cells with these inhibitors could circumvent unwanted s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00333/full |
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| author | Inna M. Yasinska Luigi Calzolai Ulrike Raap Rohanah Hussain Giuliano Siligardi Vadim V. Sumbayev Bernhard F. Gibbs Bernhard F. Gibbs |
| author_facet | Inna M. Yasinska Luigi Calzolai Ulrike Raap Rohanah Hussain Giuliano Siligardi Vadim V. Sumbayev Bernhard F. Gibbs Bernhard F. Gibbs |
| author_sort | Inna M. Yasinska |
| collection | DOAJ |
| description | Calcineurin inhibitors potentially prevent pro-allergic mediator release from basophils and mast cells but are rarely used systemically due to ubiquitous expressions of target signaling proteins. However, specific targeting of allergic effector cells with these inhibitors could circumvent unwanted side effects. We recently demonstrated the biocompatibility of gold nanoparticles (AuNPs) as a platform for non-toxic delivery of signaling inhibitors due to unique physicochemical properties of these nanomaterials. Since AuNPs can be conjugated with both anti-allergic drugs and antibodies or other proteins that specifically recognize basophils and mast cells, our aims were to assess specific targeting of allergic effector cell function using AuNPs conjugated with the calcineurin inhibitor ascomycin. Purified human basophils and LAD2 human mast cells were used for investigations with AuNPs conjugated either to CD203c antibodies or containing stem cell factor (SCF), respectively, which were amine-coupled to acidic groups of reduced glutathione (GSH). GSH was also used as a spacer for immobilization of ascomycin on the gold surface. AuNPs conjugated with anti-CD203c and ascomycin strikingly blocked IgE-dependent degranulation of both purified basophils and those present in mixed leukocyte preparations, suggesting specific targeting of these cells. In contrast, LAD2 mast cell responses were not inhibited using anti-CD203c-containing nanoconjugates but were when the conjugates contained SCF. Successful targeting of allergic effector cells using gold nanoconjugates indicates that this technology may have therapeutic potential for the treatment of allergies by specifically delivering highly effective signaling inhibitors with reduced side effects. |
| first_indexed | 2024-12-11T19:29:35Z |
| format | Article |
| id | doaj.art-3b65a95480b44f13895dedb94fdc3556 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T19:29:35Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-3b65a95480b44f13895dedb94fdc35562022-12-22T00:53:19ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-03-011010.3389/fphar.2019.00333441576Targeting of Basophil and Mast Cell Pro-Allergic Reactivity Using Functionalised Gold NanoparticlesInna M. Yasinska0Luigi Calzolai1Ulrike Raap2Rohanah Hussain3Giuliano Siligardi4Vadim V. Sumbayev5Bernhard F. Gibbs6Bernhard F. Gibbs7Medway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United KingdomEuropean Commission, Joint Research Centre, Ispra, ItalyDivision of Experimental Allergology and Immunodermatology, University of Oldenburg, Oldenburg, GermanyBeamline B23, Diamond Light Source, Didcot, United KingdomBeamline B23, Diamond Light Source, Didcot, United KingdomMedway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United KingdomMedway School of Pharmacy, Universities of Kent and Greenwich, Chatham Maritime, United KingdomDivision of Experimental Allergology and Immunodermatology, University of Oldenburg, Oldenburg, GermanyCalcineurin inhibitors potentially prevent pro-allergic mediator release from basophils and mast cells but are rarely used systemically due to ubiquitous expressions of target signaling proteins. However, specific targeting of allergic effector cells with these inhibitors could circumvent unwanted side effects. We recently demonstrated the biocompatibility of gold nanoparticles (AuNPs) as a platform for non-toxic delivery of signaling inhibitors due to unique physicochemical properties of these nanomaterials. Since AuNPs can be conjugated with both anti-allergic drugs and antibodies or other proteins that specifically recognize basophils and mast cells, our aims were to assess specific targeting of allergic effector cell function using AuNPs conjugated with the calcineurin inhibitor ascomycin. Purified human basophils and LAD2 human mast cells were used for investigations with AuNPs conjugated either to CD203c antibodies or containing stem cell factor (SCF), respectively, which were amine-coupled to acidic groups of reduced glutathione (GSH). GSH was also used as a spacer for immobilization of ascomycin on the gold surface. AuNPs conjugated with anti-CD203c and ascomycin strikingly blocked IgE-dependent degranulation of both purified basophils and those present in mixed leukocyte preparations, suggesting specific targeting of these cells. In contrast, LAD2 mast cell responses were not inhibited using anti-CD203c-containing nanoconjugates but were when the conjugates contained SCF. Successful targeting of allergic effector cells using gold nanoconjugates indicates that this technology may have therapeutic potential for the treatment of allergies by specifically delivering highly effective signaling inhibitors with reduced side effects.https://www.frontiersin.org/article/10.3389/fphar.2019.00333/fullgold nanoconjugatesbasophilsmast cellsascomycinIgECD203c |
| spellingShingle | Inna M. Yasinska Luigi Calzolai Ulrike Raap Rohanah Hussain Giuliano Siligardi Vadim V. Sumbayev Bernhard F. Gibbs Bernhard F. Gibbs Targeting of Basophil and Mast Cell Pro-Allergic Reactivity Using Functionalised Gold Nanoparticles Frontiers in Pharmacology gold nanoconjugates basophils mast cells ascomycin IgE CD203c |
| title | Targeting of Basophil and Mast Cell Pro-Allergic Reactivity Using Functionalised Gold Nanoparticles |
| title_full | Targeting of Basophil and Mast Cell Pro-Allergic Reactivity Using Functionalised Gold Nanoparticles |
| title_fullStr | Targeting of Basophil and Mast Cell Pro-Allergic Reactivity Using Functionalised Gold Nanoparticles |
| title_full_unstemmed | Targeting of Basophil and Mast Cell Pro-Allergic Reactivity Using Functionalised Gold Nanoparticles |
| title_short | Targeting of Basophil and Mast Cell Pro-Allergic Reactivity Using Functionalised Gold Nanoparticles |
| title_sort | targeting of basophil and mast cell pro allergic reactivity using functionalised gold nanoparticles |
| topic | gold nanoconjugates basophils mast cells ascomycin IgE CD203c |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00333/full |
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