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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/9/2232 |
| _version_ | 1827724465229791232 |
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| author | Luis Daniel Terrazas-Armendáriz Cynthia Aracely Alvizo-Báez Itza Eloisa Luna-Cruz Becky Annette Hernández-González Ashanti Concepción Uscanga-Palomeque Mitchel Abraham Ruiz-Robles Eduardo Gerardo Pérez Tijerina Cristina Rodríguez-Padilla Reyes Tamez-Guerra Juan Manuel Alcocer-González |
| author_facet | Luis Daniel Terrazas-Armendáriz Cynthia Aracely Alvizo-Báez Itza Eloisa Luna-Cruz Becky Annette Hernández-González Ashanti Concepción Uscanga-Palomeque Mitchel Abraham Ruiz-Robles Eduardo Gerardo Pérez Tijerina Cristina Rodríguez-Padilla Reyes Tamez-Guerra Juan Manuel Alcocer-González |
| author_sort | Luis Daniel Terrazas-Armendáriz |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T22:16:11Z |
| format | Article |
| id | doaj.art-2e44d4ea0d6945fabc06b27ed38731be |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T22:16:11Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2e44d4ea0d6945fabc06b27ed38731be2023-11-19T12:26:50ZengMDPI AGPharmaceutics1999-49232023-08-01159223210.3390/pharmaceutics15092232Systemic Delivery of Magnetogene Nanoparticle Vector for Gene Expression in Hypoxic TumorsLuis Daniel Terrazas-Armendáriz0Cynthia Aracely Alvizo-Báez1Itza Eloisa Luna-Cruz2Becky Annette Hernández-González3Ashanti Concepción Uscanga-Palomeque4Mitchel Abraham Ruiz-Robles5Eduardo Gerardo Pérez Tijerina6Cristina Rodríguez-Padilla7Reyes Tamez-Guerra8Juan Manuel Alcocer-González9Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66450, NL, MexicoLaboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66450, NL, MexicoLaboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66450, NL, MexicoLaboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66450, NL, MexicoLaboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66450, NL, MexicoCentro de Investigación en Ciencias Fisico Matematicas, Facultad de Ciencias Físico Matematicas, Universidad Autónoma de Nuevo León, Ciudad Universitaria, San Nicolás de los Garza 66451, NL, MexicoCentro de Investigación en Ciencias Fisico Matematicas, Facultad de Ciencias Físico Matematicas, Universidad Autónoma de Nuevo León, Ciudad Universitaria, San Nicolás de los Garza 66451, NL, MexicoLaboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66450, NL, MexicoLaboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66450, NL, MexicoLaboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66450, NL, MexicoCancer 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.https://www.mdpi.com/1999-4923/15/9/2232Magnetogenemagnetic nanoparticlesmagnetofectionhypoxiachitosangene expression |
| spellingShingle | Luis Daniel Terrazas-Armendáriz Cynthia Aracely Alvizo-Báez Itza Eloisa Luna-Cruz Becky Annette Hernández-González Ashanti Concepción Uscanga-Palomeque Mitchel Abraham Ruiz-Robles Eduardo Gerardo Pérez Tijerina Cristina Rodríguez-Padilla Reyes Tamez-Guerra Juan Manuel Alcocer-González Systemic Delivery of Magnetogene Nanoparticle Vector for Gene Expression in Hypoxic Tumors Pharmaceutics Magnetogene magnetic nanoparticles magnetofection hypoxia chitosan gene expression |
| 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 | Magnetogene magnetic nanoparticles magnetofection hypoxia chitosan gene expression |
| url | https://www.mdpi.com/1999-4923/15/9/2232 |
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