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Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer
BACKGROUND: Tamoxifen is the standard endocrine therapy for breast cancers, which require metabolic activation by cytochrome P450 enzymes (CYP). However, the lower and variable concentrations of CYP activity at the tumor remain major bottlenecks for the efficient treatment, causing severe side-effec...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819296/ https://www.ncbi.nlm.nih.gov/pubmed/29463260 http://dx.doi.org/10.1186/s12951-018-0345-2 |
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author | Chauhan, Kanchan Hernandez-Meza, Juan M. Rodríguez-Hernández, Ana G. Juarez-Moreno, Karla Sengar, Prakhar Vazquez-Duhalt, Rafael |
author_facet | Chauhan, Kanchan Hernandez-Meza, Juan M. Rodríguez-Hernández, Ana G. Juarez-Moreno, Karla Sengar, Prakhar Vazquez-Duhalt, Rafael |
author_sort | Chauhan, Kanchan |
collection | PubMed |
description | BACKGROUND: Tamoxifen is the standard endocrine therapy for breast cancers, which require metabolic activation by cytochrome P450 enzymes (CYP). However, the lower and variable concentrations of CYP activity at the tumor remain major bottlenecks for the efficient treatment, causing severe side-effects. Combination nanotherapy has gained much recent attention for cancer treatment as it reduces the drug-associated toxicity without affecting the therapeutic response. RESULTS: Here we show the modular design of P22 bacteriophage virus-like particles for nanoscale integration of virus-driven enzyme prodrug therapy and photodynamic therapy. These virus capsids carrying CYP activity at the core are decorated with photosensitizer and targeting moiety at the surface for effective combinatory treatment. The estradiol-functionalized nanoparticles are recognized and internalized into ER+ breast tumor cells increasing the intracellular CYP activity and showing the ability to produce reactive oxygen species (ROS) upon UV(365 nm) irradiation. The generated ROS in synergy with enzymatic activity drastically enhanced the tamoxifen sensitivity in vitro, strongly inhibiting tumor cells. CONCLUSIONS: This work clearly demonstrated that the targeted combinatory treatment using multifunctional biocatalytic P22 represents the effective nanotherapeutics for ER+ breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12951-018-0345-2) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5819296 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58192962018-02-21 Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer Chauhan, Kanchan Hernandez-Meza, Juan M. Rodríguez-Hernández, Ana G. Juarez-Moreno, Karla Sengar, Prakhar Vazquez-Duhalt, Rafael J Nanobiotechnology Research BACKGROUND: Tamoxifen is the standard endocrine therapy for breast cancers, which require metabolic activation by cytochrome P450 enzymes (CYP). However, the lower and variable concentrations of CYP activity at the tumor remain major bottlenecks for the efficient treatment, causing severe side-effects. Combination nanotherapy has gained much recent attention for cancer treatment as it reduces the drug-associated toxicity without affecting the therapeutic response. RESULTS: Here we show the modular design of P22 bacteriophage virus-like particles for nanoscale integration of virus-driven enzyme prodrug therapy and photodynamic therapy. These virus capsids carrying CYP activity at the core are decorated with photosensitizer and targeting moiety at the surface for effective combinatory treatment. The estradiol-functionalized nanoparticles are recognized and internalized into ER+ breast tumor cells increasing the intracellular CYP activity and showing the ability to produce reactive oxygen species (ROS) upon UV(365 nm) irradiation. The generated ROS in synergy with enzymatic activity drastically enhanced the tamoxifen sensitivity in vitro, strongly inhibiting tumor cells. CONCLUSIONS: This work clearly demonstrated that the targeted combinatory treatment using multifunctional biocatalytic P22 represents the effective nanotherapeutics for ER+ breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12951-018-0345-2) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-20 /pmc/articles/PMC5819296/ /pubmed/29463260 http://dx.doi.org/10.1186/s12951-018-0345-2 Text en © The Author(s) 2018 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 Chauhan, Kanchan Hernandez-Meza, Juan M. Rodríguez-Hernández, Ana G. Juarez-Moreno, Karla Sengar, Prakhar Vazquez-Duhalt, Rafael Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer |
title | Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer |
title_full | Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer |
title_fullStr | Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer |
title_full_unstemmed | Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer |
title_short | Multifunctionalized biocatalytic P22 nanoreactor for combinatory treatment of ER+ breast cancer |
title_sort | multifunctionalized biocatalytic p22 nanoreactor for combinatory treatment of er+ breast cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819296/ https://www.ncbi.nlm.nih.gov/pubmed/29463260 http://dx.doi.org/10.1186/s12951-018-0345-2 |
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