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Bio-Orthogonal Chemistry and Reloadable Biomaterial Enable Local Activation of Antibiotic Prodrugs and Enhance Treatments against Staphylococcus aureus Infections
[Image: see text] Systemic administration of antibiotics can cause severe side-effects such as liver and kidney toxicity, destruction of healthy gut bacteria, as well as multidrug resistance. Here, we present a bio-orthogonal chemistry-based strategy toward local prodrug concentration and activation...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311693/ https://www.ncbi.nlm.nih.gov/pubmed/30648146 http://dx.doi.org/10.1021/acscentsci.8b00344 |
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author | Czuban, Magdalena Srinivasan, Sangeetha Yee, Nathan A. Agustin, Edgar Koliszak, Anna Miller, Ethan Khan, Irfan Quinones, Ilenis Noory, Hasina Motola, Christopher Volkmer, Rudolf Di Luca, Mariagrazia Trampuz, Andrej Royzen, Maksim Mejia Oneto, Jose M. |
author_facet | Czuban, Magdalena Srinivasan, Sangeetha Yee, Nathan A. Agustin, Edgar Koliszak, Anna Miller, Ethan Khan, Irfan Quinones, Ilenis Noory, Hasina Motola, Christopher Volkmer, Rudolf Di Luca, Mariagrazia Trampuz, Andrej Royzen, Maksim Mejia Oneto, Jose M. |
author_sort | Czuban, Magdalena |
collection | PubMed |
description | [Image: see text] Systemic administration of antibiotics can cause severe side-effects such as liver and kidney toxicity, destruction of healthy gut bacteria, as well as multidrug resistance. Here, we present a bio-orthogonal chemistry-based strategy toward local prodrug concentration and activation. The strategy is based on the inverse electron-demand Diels–Alder chemistry between trans-cyclooctene and tetrazine and involves a biomaterial that can concentrate and activate multiple doses of systemic antibiotic therapy prodrugs at a local site. We demonstrate that a biomaterial, consisting of alginate hydrogel modified with tetrazine, is efficient at activating multiple doses of prodrugs of vancomycin and daptomycin in vitro as well as in vivo. These results support a drug delivery process that is independent of endogenous environmental markers. This approach is expected to improve therapeutic efficacy with decreased side-effects of antibiotics against bacterial infections. The platform has a wide scope of possible applications such as wound healing, and cancer and immunotherapy. |
format | Online Article Text |
id | pubmed-6311693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-63116932019-01-15 Bio-Orthogonal Chemistry and Reloadable Biomaterial Enable Local Activation of Antibiotic Prodrugs and Enhance Treatments against Staphylococcus aureus Infections Czuban, Magdalena Srinivasan, Sangeetha Yee, Nathan A. Agustin, Edgar Koliszak, Anna Miller, Ethan Khan, Irfan Quinones, Ilenis Noory, Hasina Motola, Christopher Volkmer, Rudolf Di Luca, Mariagrazia Trampuz, Andrej Royzen, Maksim Mejia Oneto, Jose M. ACS Cent Sci [Image: see text] Systemic administration of antibiotics can cause severe side-effects such as liver and kidney toxicity, destruction of healthy gut bacteria, as well as multidrug resistance. Here, we present a bio-orthogonal chemistry-based strategy toward local prodrug concentration and activation. The strategy is based on the inverse electron-demand Diels–Alder chemistry between trans-cyclooctene and tetrazine and involves a biomaterial that can concentrate and activate multiple doses of systemic antibiotic therapy prodrugs at a local site. We demonstrate that a biomaterial, consisting of alginate hydrogel modified with tetrazine, is efficient at activating multiple doses of prodrugs of vancomycin and daptomycin in vitro as well as in vivo. These results support a drug delivery process that is independent of endogenous environmental markers. This approach is expected to improve therapeutic efficacy with decreased side-effects of antibiotics against bacterial infections. The platform has a wide scope of possible applications such as wound healing, and cancer and immunotherapy. American Chemical Society 2018-12-12 2018-12-26 /pmc/articles/PMC6311693/ /pubmed/30648146 http://dx.doi.org/10.1021/acscentsci.8b00344 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Czuban, Magdalena Srinivasan, Sangeetha Yee, Nathan A. Agustin, Edgar Koliszak, Anna Miller, Ethan Khan, Irfan Quinones, Ilenis Noory, Hasina Motola, Christopher Volkmer, Rudolf Di Luca, Mariagrazia Trampuz, Andrej Royzen, Maksim Mejia Oneto, Jose M. Bio-Orthogonal Chemistry and Reloadable Biomaterial Enable Local Activation of Antibiotic Prodrugs and Enhance Treatments against Staphylococcus aureus Infections |
title | Bio-Orthogonal Chemistry and Reloadable Biomaterial
Enable Local Activation of Antibiotic Prodrugs and Enhance Treatments
against Staphylococcus aureus Infections |
title_full | Bio-Orthogonal Chemistry and Reloadable Biomaterial
Enable Local Activation of Antibiotic Prodrugs and Enhance Treatments
against Staphylococcus aureus Infections |
title_fullStr | Bio-Orthogonal Chemistry and Reloadable Biomaterial
Enable Local Activation of Antibiotic Prodrugs and Enhance Treatments
against Staphylococcus aureus Infections |
title_full_unstemmed | Bio-Orthogonal Chemistry and Reloadable Biomaterial
Enable Local Activation of Antibiotic Prodrugs and Enhance Treatments
against Staphylococcus aureus Infections |
title_short | Bio-Orthogonal Chemistry and Reloadable Biomaterial
Enable Local Activation of Antibiotic Prodrugs and Enhance Treatments
against Staphylococcus aureus Infections |
title_sort | bio-orthogonal chemistry and reloadable biomaterial
enable local activation of antibiotic prodrugs and enhance treatments
against staphylococcus aureus infections |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311693/ https://www.ncbi.nlm.nih.gov/pubmed/30648146 http://dx.doi.org/10.1021/acscentsci.8b00344 |
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