Modification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications

Background: Tumor-targeting bacteriophages can be used as a versatile new platform for the delivery of diagnostic imaging agents and therapeutic cargo. This became possible due to the development of viral capsid modification method. Earlier in our laboratory and using phage display technology, phage...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Maya Alexandrovna Dymova, Yaroslav Alexandrovich Utkin, Maria Denisovna Dmitrieva, Elena Vladimirovna Kuligina, Vladimir Alexandrovich Richter
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	MDA-MB 231 cells tumor-targeting bacteriophages chemical modification of bacteriophages FAM–NHS theranostic drugs Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/b09de5a7df9e4c7994f631e3c7696a02
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:b09de5a7df9e4c7994f631e3c7696a02
record_format	dspace
spelling	oai:doaj.org-article:b09de5a7df9e4c7994f631e3c7696a022021-11-11T18:32:48ZModification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications10.3390/molecules262165641420-3049https://doaj.org/article/b09de5a7df9e4c7994f631e3c7696a022021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6564https://doaj.org/toc/1420-3049Background: Tumor-targeting bacteriophages can be used as a versatile new platform for the delivery of diagnostic imaging agents and therapeutic cargo. This became possible due to the development of viral capsid modification method. Earlier in our laboratory and using phage display technology, phages to malignant breast cancer cells MDA-MB 231 were obtained. The goal of this study was the optimization of phage modification and the assessment of the effect of the latter on the efficiency of phage particle penetration into MDA-MB 231 cells. Methods: In this work, we used several methods, such as chemical phage modification using FAM-NHS ester, spectrophotometry, phage amplification, sequencing, phage titration, flow cytometry, and confocal microscopy. Results: We performed chemical phage modification using different concentrations of FAM-NHS dye (0.5 mM, 1 mM, 2 mM, 4 mM, 8 mM). It was shown that with an increase of the modification degree, the phage titer decreases. The maximum modification coefficient of the phage envelope with the FAM–NHS dye was observed with 4 mM modifying agent and had approximately 804,2 FAM molecules per phage. Through the immunofluorescence staining and flow cytometry methods, it was shown that the modified bacteriophage retains the ability to internalize into MDA-MB-231 cells. The estimation of the number of phages that could have penetrated into one tumor cell was conducted. Conclusions: Optimizing the conditions for phage modification can be an effective strategy for producing tumor-targeting diagnostic and therapeutic agents, i.e., theranostic drugs.Maya Alexandrovna DymovaYaroslav Alexandrovich UtkinMaria Denisovna DmitrievaElena Vladimirovna KuliginaVladimir Alexandrovich RichterMDPI AGarticleMDA-MB 231 cellstumor-targeting bacteriophageschemical modification of bacteriophagesFAM–NHStheranostic drugsOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6564, p 6564 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	MDA-MB 231 cells tumor-targeting bacteriophages chemical modification of bacteriophages FAM–NHS theranostic drugs Organic chemistry QD241-441
spellingShingle	MDA-MB 231 cells tumor-targeting bacteriophages chemical modification of bacteriophages FAM–NHS theranostic drugs Organic chemistry QD241-441 Maya Alexandrovna Dymova Yaroslav Alexandrovich Utkin Maria Denisovna Dmitrieva Elena Vladimirovna Kuligina Vladimir Alexandrovich Richter Modification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications
description	Background: Tumor-targeting bacteriophages can be used as a versatile new platform for the delivery of diagnostic imaging agents and therapeutic cargo. This became possible due to the development of viral capsid modification method. Earlier in our laboratory and using phage display technology, phages to malignant breast cancer cells MDA-MB 231 were obtained. The goal of this study was the optimization of phage modification and the assessment of the effect of the latter on the efficiency of phage particle penetration into MDA-MB 231 cells. Methods: In this work, we used several methods, such as chemical phage modification using FAM-NHS ester, spectrophotometry, phage amplification, sequencing, phage titration, flow cytometry, and confocal microscopy. Results: We performed chemical phage modification using different concentrations of FAM-NHS dye (0.5 mM, 1 mM, 2 mM, 4 mM, 8 mM). It was shown that with an increase of the modification degree, the phage titer decreases. The maximum modification coefficient of the phage envelope with the FAM–NHS dye was observed with 4 mM modifying agent and had approximately 804,2 FAM molecules per phage. Through the immunofluorescence staining and flow cytometry methods, it was shown that the modified bacteriophage retains the ability to internalize into MDA-MB-231 cells. The estimation of the number of phages that could have penetrated into one tumor cell was conducted. Conclusions: Optimizing the conditions for phage modification can be an effective strategy for producing tumor-targeting diagnostic and therapeutic agents, i.e., theranostic drugs.
format	article
author	Maya Alexandrovna Dymova Yaroslav Alexandrovich Utkin Maria Denisovna Dmitrieva Elena Vladimirovna Kuligina Vladimir Alexandrovich Richter
author_facet	Maya Alexandrovna Dymova Yaroslav Alexandrovich Utkin Maria Denisovna Dmitrieva Elena Vladimirovna Kuligina Vladimir Alexandrovich Richter
author_sort	Maya Alexandrovna Dymova
title	Modification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications
title_short	Modification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications
title_full	Modification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications
title_fullStr	Modification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications
title_full_unstemmed	Modification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications
title_sort	modification of a tumor-targeting bacteriophage for potential diagnostic applications
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/b09de5a7df9e4c7994f631e3c7696a02
work_keys_str_mv	AT mayaalexandrovnadymova modificationofatumortargetingbacteriophageforpotentialdiagnosticapplications AT yaroslavalexandrovichutkin modificationofatumortargetingbacteriophageforpotentialdiagnosticapplications AT mariadenisovnadmitrieva modificationofatumortargetingbacteriophageforpotentialdiagnosticapplications AT elenavladimirovnakuligina modificationofatumortargetingbacteriophageforpotentialdiagnosticapplications AT vladimiralexandrovichrichter modificationofatumortargetingbacteriophageforpotentialdiagnosticapplications
_version_	1718431780921409536

Modification of a Tumor-Targeting Bacteriophage for Potential Diagnostic Applications

Ejemplares similares