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Systemic Delivery of Magnetogene Nanoparticle Vector for Gene Expression in Hypoxic Tumors
Cancer is a disease that causes millions of deaths per year worldwide because conventional treatments have disadvantages such as unspecific tumor selectivity and unwanted toxicity. Most human solid tumors present hypoxic microenvironments and this promotes multidrug resistance. In this study, we pre...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536535/ https://www.ncbi.nlm.nih.gov/pubmed/37765201 http://dx.doi.org/10.3390/pharmaceutics15092232 |
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author | Terrazas-Armendáriz, Luis Daniel Alvizo-Báez, Cynthia Aracely Luna-Cruz, Itza Eloisa Hernández-González, Becky Annette Uscanga-Palomeque, Ashanti Concepción Ruiz-Robles, Mitchel Abraham Pérez Tijerina, Eduardo Gerardo Rodríguez-Padilla, Cristina Tamez-Guerra, Reyes Alcocer-González, Juan Manuel |
author_facet | Terrazas-Armendáriz, Luis Daniel Alvizo-Báez, Cynthia Aracely Luna-Cruz, Itza Eloisa Hernández-González, Becky Annette Uscanga-Palomeque, Ashanti Concepción Ruiz-Robles, Mitchel Abraham Pérez Tijerina, Eduardo Gerardo Rodríguez-Padilla, Cristina Tamez-Guerra, Reyes Alcocer-González, Juan Manuel |
author_sort | Terrazas-Armendáriz, Luis Daniel |
collection | PubMed |
description | Cancer is a disease that causes millions of deaths per year worldwide because conventional treatments have disadvantages such as unspecific tumor selectivity and unwanted toxicity. Most human solid tumors present hypoxic microenvironments and this promotes multidrug resistance. In this study, we present “Magnetogene nanoparticle vector” which takes advantage of the hypoxic microenvironment of solid tumors to increase selective gene expression in tumor cells and reduce unwanted toxicity in healthy cells; this vector was guided by a magnet to the tumor tissue. Magnetic nanoparticles (MNPs), chitosan (CS), and the pHRE-Luc plasmid with a hypoxia-inducible promoter were used to synthesize the vector called “Magnetogene nanoparticles” by ionic gelation. The hypoxic functionality of Magnetogene vector nanoparticles was confirmed in the B16F10 cell line by measuring the expression of the luciferase reporter gene under hypoxic and normoxic conditions. Also, the efficiency of the Magnetogene vector was confirmed in vivo. Magnetogene was administered by intravenous injection (IV) in the tail vein and directed through an external magnetic field at the site of tumor growth in C57Bl/6 mice. A Magnetogene vector with a size of 50 to 70 nm was directed and retained at the tumor area and gene expression was higher at the tumor site than in the others tissues, confirming the selectivity of this vector towards hypoxic tumor areas. This nanosystem, that we called the “Magnetogene vector” for systemic delivery and specific gene expression in hypoxic tumors controlled by an external magnetic designed to target hypoxic regions of tumors, can be used for cancer-specific gene therapies. |
format | Online Article Text |
id | pubmed-10536535 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105365352023-09-29 Systemic Delivery of Magnetogene Nanoparticle Vector for Gene Expression in Hypoxic Tumors Terrazas-Armendáriz, Luis Daniel Alvizo-Báez, Cynthia Aracely Luna-Cruz, Itza Eloisa Hernández-González, Becky Annette Uscanga-Palomeque, Ashanti Concepción Ruiz-Robles, Mitchel Abraham Pérez Tijerina, Eduardo Gerardo Rodríguez-Padilla, Cristina Tamez-Guerra, Reyes Alcocer-González, Juan Manuel Pharmaceutics Article Cancer is a disease that causes millions of deaths per year worldwide because conventional treatments have disadvantages such as unspecific tumor selectivity and unwanted toxicity. Most human solid tumors present hypoxic microenvironments and this promotes multidrug resistance. In this study, we present “Magnetogene nanoparticle vector” which takes advantage of the hypoxic microenvironment of solid tumors to increase selective gene expression in tumor cells and reduce unwanted toxicity in healthy cells; this vector was guided by a magnet to the tumor tissue. Magnetic nanoparticles (MNPs), chitosan (CS), and the pHRE-Luc plasmid with a hypoxia-inducible promoter were used to synthesize the vector called “Magnetogene nanoparticles” by ionic gelation. The hypoxic functionality of Magnetogene vector nanoparticles was confirmed in the B16F10 cell line by measuring the expression of the luciferase reporter gene under hypoxic and normoxic conditions. Also, the efficiency of the Magnetogene vector was confirmed in vivo. Magnetogene was administered by intravenous injection (IV) in the tail vein and directed through an external magnetic field at the site of tumor growth in C57Bl/6 mice. A Magnetogene vector with a size of 50 to 70 nm was directed and retained at the tumor area and gene expression was higher at the tumor site than in the others tissues, confirming the selectivity of this vector towards hypoxic tumor areas. This nanosystem, that we called the “Magnetogene vector” for systemic delivery and specific gene expression in hypoxic tumors controlled by an external magnetic designed to target hypoxic regions of tumors, can be used for cancer-specific gene therapies. MDPI 2023-08-29 /pmc/articles/PMC10536535/ /pubmed/37765201 http://dx.doi.org/10.3390/pharmaceutics15092232 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Terrazas-Armendáriz, Luis Daniel Alvizo-Báez, Cynthia Aracely Luna-Cruz, Itza Eloisa Hernández-González, Becky Annette Uscanga-Palomeque, Ashanti Concepción Ruiz-Robles, Mitchel Abraham Pérez Tijerina, Eduardo Gerardo Rodríguez-Padilla, Cristina Tamez-Guerra, Reyes Alcocer-González, Juan Manuel Systemic Delivery of Magnetogene Nanoparticle Vector for Gene Expression in Hypoxic Tumors |
title | Systemic Delivery of Magnetogene Nanoparticle Vector for Gene Expression in Hypoxic Tumors |
title_full | Systemic Delivery of Magnetogene Nanoparticle Vector for Gene Expression in Hypoxic Tumors |
title_fullStr | Systemic Delivery of Magnetogene Nanoparticle Vector for Gene Expression in Hypoxic Tumors |
title_full_unstemmed | Systemic Delivery of Magnetogene Nanoparticle Vector for Gene Expression in Hypoxic Tumors |
title_short | Systemic Delivery of Magnetogene Nanoparticle Vector for Gene Expression in Hypoxic Tumors |
title_sort | systemic delivery of magnetogene nanoparticle vector for gene expression in hypoxic tumors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10536535/ https://www.ncbi.nlm.nih.gov/pubmed/37765201 http://dx.doi.org/10.3390/pharmaceutics15092232 |
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