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
Laboratorio de Inmunología y Virología, Facultad de Ciencias Biológicas, Universidad Autónoma de Nuevo León, San Nicolás de los Garza 66450, NL, Mexico.
Centro 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, Mexico.
Pharmaceutics. 2023 Aug 29;15(9):2232. doi: 10.3390/pharmaceutics15092232.
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.
癌症是一种每年在全球导致数百万人死亡的疾病，因为传统治疗方法存在诸如肿瘤选择性不特异和存在不良毒性等缺点。大多数人类实体瘤呈现缺氧微环境，这会促进多药耐药性。在本研究中，我们展示了“磁基因纳米颗粒载体”，它利用实体瘤的缺氧微环境来增加肿瘤细胞中的选择性基因表达，并降低健康细胞中的不良毒性；该载体通过磁场引导至肿瘤组织。使用磁性纳米颗粒（MNPs）、壳聚糖（CS）和带有缺氧诱导启动子的pHRE-Luc质粒，通过离子凝胶化合成了称为“磁基因纳米颗粒”的载体。通过在缺氧和正常氧条件下测量荧光素酶报告基因的表达，在B16F10细胞系中证实了磁基因载体纳米颗粒的缺氧功能。此外，还在体内证实了磁基因载体的效率。通过尾静脉静脉注射（IV）给予磁基因，并通过外部磁场将其引导至C57Bl/6小鼠肿瘤生长部位。大小为50至70nm的磁基因载体被引导并保留在肿瘤区域，肿瘤部位的基因表达高于其他组织，证实了该载体对缺氧肿瘤区域的选择性。这种纳米系统，我们称之为“磁基因载体”，用于通过外部磁场控制的全身递送和在缺氧肿瘤中的特异性基因表达，旨在靶向肿瘤的缺氧区域，可用于癌症特异性基因治疗。
