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Design of a VLP-nanovehicle for CYP450 enzymatic activity delivery

BACKGROUND: The intracellular delivery of enzymes for therapeutic use has a promising future for the treatment of several diseases such as genetic disorders and cancer. Virus-like particles offer an interesting platform for enzymatic delivery to targeted cells because of their great cargo capacity a...

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Autores principales: Sánchez-Sánchez, Lorena, Tapia-Moreno, Alejandro, Juarez-Moreno, Karla, Patterson, Dustin P., Cadena-Nava, Ruben D., Douglas, Trevor, Vazquez-Duhalt, Rafael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599659/
https://www.ncbi.nlm.nih.gov/pubmed/26452461
http://dx.doi.org/10.1186/s12951-015-0127-z
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author Sánchez-Sánchez, Lorena
Tapia-Moreno, Alejandro
Juarez-Moreno, Karla
Patterson, Dustin P.
Cadena-Nava, Ruben D.
Douglas, Trevor
Vazquez-Duhalt, Rafael
author_facet Sánchez-Sánchez, Lorena
Tapia-Moreno, Alejandro
Juarez-Moreno, Karla
Patterson, Dustin P.
Cadena-Nava, Ruben D.
Douglas, Trevor
Vazquez-Duhalt, Rafael
author_sort Sánchez-Sánchez, Lorena
collection PubMed
description BACKGROUND: The intracellular delivery of enzymes for therapeutic use has a promising future for the treatment of several diseases such as genetic disorders and cancer. Virus-like particles offer an interesting platform for enzymatic delivery to targeted cells because of their great cargo capacity and the enhancement of the biocatalyst stability towards several factors important in the practical application of these nanoparticles. RESULTS: We have designed a nano-bioreactor based on the encapsulation of a cytochrome P450 (CYP) inside the capsid derived from the bacteriophage P22. An enhanced peroxigenase, CYPBM3, was selected as a model enzyme because of its potential in enzyme prodrug therapy. A total of 109 enzymes per capsid were encapsulated with a 70 % retention of activity for cytochromes with the correct incorporation of the heme cofactor. Upon encapsulation, the stability of the enzyme towards protease degradation and acidic pH was increased. Cytochrome P450 activity was delivered into Human cervix carcinoma cells via transfecting P22-CYP nanoparticles with lipofectamine. CONCLUSION: This work provides a clear demonstration of the potential of biocatalytic virus-like particles as medical relevant enzymatic delivery vehicles for clinical applications.
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spelling pubmed-45996592015-10-10 Design of a VLP-nanovehicle for CYP450 enzymatic activity delivery Sánchez-Sánchez, Lorena Tapia-Moreno, Alejandro Juarez-Moreno, Karla Patterson, Dustin P. Cadena-Nava, Ruben D. Douglas, Trevor Vazquez-Duhalt, Rafael J Nanobiotechnology Research BACKGROUND: The intracellular delivery of enzymes for therapeutic use has a promising future for the treatment of several diseases such as genetic disorders and cancer. Virus-like particles offer an interesting platform for enzymatic delivery to targeted cells because of their great cargo capacity and the enhancement of the biocatalyst stability towards several factors important in the practical application of these nanoparticles. RESULTS: We have designed a nano-bioreactor based on the encapsulation of a cytochrome P450 (CYP) inside the capsid derived from the bacteriophage P22. An enhanced peroxigenase, CYPBM3, was selected as a model enzyme because of its potential in enzyme prodrug therapy. A total of 109 enzymes per capsid were encapsulated with a 70 % retention of activity for cytochromes with the correct incorporation of the heme cofactor. Upon encapsulation, the stability of the enzyme towards protease degradation and acidic pH was increased. Cytochrome P450 activity was delivered into Human cervix carcinoma cells via transfecting P22-CYP nanoparticles with lipofectamine. CONCLUSION: This work provides a clear demonstration of the potential of biocatalytic virus-like particles as medical relevant enzymatic delivery vehicles for clinical applications. BioMed Central 2015-10-09 /pmc/articles/PMC4599659/ /pubmed/26452461 http://dx.doi.org/10.1186/s12951-015-0127-z Text en © Sánchez-Sánchez et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Sánchez-Sánchez, Lorena
Tapia-Moreno, Alejandro
Juarez-Moreno, Karla
Patterson, Dustin P.
Cadena-Nava, Ruben D.
Douglas, Trevor
Vazquez-Duhalt, Rafael
Design of a VLP-nanovehicle for CYP450 enzymatic activity delivery
title Design of a VLP-nanovehicle for CYP450 enzymatic activity delivery
title_full Design of a VLP-nanovehicle for CYP450 enzymatic activity delivery
title_fullStr Design of a VLP-nanovehicle for CYP450 enzymatic activity delivery
title_full_unstemmed Design of a VLP-nanovehicle for CYP450 enzymatic activity delivery
title_short Design of a VLP-nanovehicle for CYP450 enzymatic activity delivery
title_sort design of a vlp-nanovehicle for cyp450 enzymatic activity delivery
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599659/
https://www.ncbi.nlm.nih.gov/pubmed/26452461
http://dx.doi.org/10.1186/s12951-015-0127-z
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