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Characteristics and Stability Assessment of Therapeutic Methionine γ-lyase-Loaded Polyionic Vesicles
[Image: see text] Pyridoxal 5′-phosphate-dependent methionine γ-lyase from Citrobacter freundii (MGL, EC 4.4.1.11) is studied as an antitumor enzyme and in combination with substrates as an antibacterial agent in enzyme pro-drug therapy. For the possibility of in vivo trials, two mutant forms, C115H...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757458/ https://www.ncbi.nlm.nih.gov/pubmed/35036759 http://dx.doi.org/10.1021/acsomega.1c05558 |
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author | Koval, Vasily Morozova, Elena Revtovich, Svetlana Lyfenko, Anna Chobanian, Arpi Timofeeva, Viktoria Solovieva, Anna Anufrieva, Natalya Kulikova, Vitalia Demidkina, Tatyana |
author_facet | Koval, Vasily Morozova, Elena Revtovich, Svetlana Lyfenko, Anna Chobanian, Arpi Timofeeva, Viktoria Solovieva, Anna Anufrieva, Natalya Kulikova, Vitalia Demidkina, Tatyana |
author_sort | Koval, Vasily |
collection | PubMed |
description | [Image: see text] Pyridoxal 5′-phosphate-dependent methionine γ-lyase from Citrobacter freundii (MGL, EC 4.4.1.11) is studied as an antitumor enzyme and in combination with substrates as an antibacterial agent in enzyme pro-drug therapy. For the possibility of in vivo trials, two mutant forms, C115H MGL and V358Y MGL, were encapsulated into polyionic vesicles (PICsomes). Five pairs of polymers with the number of polymer chain units 20, 50, 70, 120, and 160 were synthesized. The effect of polymer length—PEGylated poly-l-aspartic acid and poly-l-lysine—on the degree of MGL incorporation into PICsomes and their size was investigated. Encapsulation of proteins in PICsomes is a rather new technique. Our data demonstrated that the length of the polymers and, therefore, the ratio of the hydrophobic and hydrophilic fragments most likely should be selected individually for each protein to be encapsulated. The efficiency of encapsulation of MGL mutant forms into PICsomes was up to 11%. The hydrodynamic diameter and surface potential of hollow and MGL-loaded PICsomes were evaluated by the dynamic light scattering method. The size and morphology of the PICsomes were determined by atomic force microscopy. The most acceptable for further in vivo studies were PICsomes(20) with a size of 57–64 nm, PICsomes(70) of 50–90 nm, and PICsomes(120) of 100–105 nm. The analysis of the steady-state parameters has demonstrated that both mutant forms retained their catalytic properties inside the nanoparticles. The release study of the enzymes from PICsomes revealed that about 50% of the enzymes remained encapsulated in PICsomes(70) and PICsomes(120) after 24 h. Based on the data obtained, the most promising for in vivo studies are PICsomes(70) and PICsomes(120.) |
format | Online Article Text |
id | pubmed-8757458 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-87574582022-01-14 Characteristics and Stability Assessment of Therapeutic Methionine γ-lyase-Loaded Polyionic Vesicles Koval, Vasily Morozova, Elena Revtovich, Svetlana Lyfenko, Anna Chobanian, Arpi Timofeeva, Viktoria Solovieva, Anna Anufrieva, Natalya Kulikova, Vitalia Demidkina, Tatyana ACS Omega [Image: see text] Pyridoxal 5′-phosphate-dependent methionine γ-lyase from Citrobacter freundii (MGL, EC 4.4.1.11) is studied as an antitumor enzyme and in combination with substrates as an antibacterial agent in enzyme pro-drug therapy. For the possibility of in vivo trials, two mutant forms, C115H MGL and V358Y MGL, were encapsulated into polyionic vesicles (PICsomes). Five pairs of polymers with the number of polymer chain units 20, 50, 70, 120, and 160 were synthesized. The effect of polymer length—PEGylated poly-l-aspartic acid and poly-l-lysine—on the degree of MGL incorporation into PICsomes and their size was investigated. Encapsulation of proteins in PICsomes is a rather new technique. Our data demonstrated that the length of the polymers and, therefore, the ratio of the hydrophobic and hydrophilic fragments most likely should be selected individually for each protein to be encapsulated. The efficiency of encapsulation of MGL mutant forms into PICsomes was up to 11%. The hydrodynamic diameter and surface potential of hollow and MGL-loaded PICsomes were evaluated by the dynamic light scattering method. The size and morphology of the PICsomes were determined by atomic force microscopy. The most acceptable for further in vivo studies were PICsomes(20) with a size of 57–64 nm, PICsomes(70) of 50–90 nm, and PICsomes(120) of 100–105 nm. The analysis of the steady-state parameters has demonstrated that both mutant forms retained their catalytic properties inside the nanoparticles. The release study of the enzymes from PICsomes revealed that about 50% of the enzymes remained encapsulated in PICsomes(70) and PICsomes(120) after 24 h. Based on the data obtained, the most promising for in vivo studies are PICsomes(70) and PICsomes(120.) American Chemical Society 2021-12-27 /pmc/articles/PMC8757458/ /pubmed/35036759 http://dx.doi.org/10.1021/acsomega.1c05558 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Koval, Vasily Morozova, Elena Revtovich, Svetlana Lyfenko, Anna Chobanian, Arpi Timofeeva, Viktoria Solovieva, Anna Anufrieva, Natalya Kulikova, Vitalia Demidkina, Tatyana Characteristics and Stability Assessment of Therapeutic Methionine γ-lyase-Loaded Polyionic Vesicles |
title | Characteristics and Stability Assessment of Therapeutic
Methionine γ-lyase-Loaded Polyionic Vesicles |
title_full | Characteristics and Stability Assessment of Therapeutic
Methionine γ-lyase-Loaded Polyionic Vesicles |
title_fullStr | Characteristics and Stability Assessment of Therapeutic
Methionine γ-lyase-Loaded Polyionic Vesicles |
title_full_unstemmed | Characteristics and Stability Assessment of Therapeutic
Methionine γ-lyase-Loaded Polyionic Vesicles |
title_short | Characteristics and Stability Assessment of Therapeutic
Methionine γ-lyase-Loaded Polyionic Vesicles |
title_sort | characteristics and stability assessment of therapeutic
methionine γ-lyase-loaded polyionic vesicles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757458/ https://www.ncbi.nlm.nih.gov/pubmed/35036759 http://dx.doi.org/10.1021/acsomega.1c05558 |
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