Pool Héctor, Campos-Vega Rocio, Herrera-Hernández María Guadalupe, García-Solis Pablo, García-Gasca Teresa, Sánchez Isaac Cornelius, Luna-Bárcenas Gabriel, Vergara-Castañeda Haydé
Centro de Investigaciones y Estudios Avanzados (CINVESTAV) del Instituto Politécnico Nacional, Unidad Querétaro Juriquilla, Querétaro 76230, México.
Departamento de Investigación y Posgrado en Alimentos, Facultad de Química, Universidad Autónoma de Querétaro Querétaro 76010. México.
Am J Transl Res. 2018 Aug 15;10(8):2306-2323. eCollection 2018.
The anticancer use of genistein (Gen) has been severely limited due to its low water solubility, low bioavailability, and instability under experimental conditions. To overcome these limitations, we propose a formulation of a hybrid nanomaterial (HNM) based upon the incorporation of Gen into PEGylated silica nanoparticles (PEG-SiNPs) (Gen-PEG-SiHNM), where their physicochemical and biological effects on HT29 cells were evaluated. Genistein-loaded PEGylated silica hybrid nanomaterials were obtained by a simple end effective aqueous dispersion method. Physicochemical properties were determined by its mean particle size, surface charge, amount of cargo, spectroscopic properties, release profiles and aqueous solubility. biological performance was carried out by evaluating its antioxidant capacity and elucidating its antiproliferative mechanistic. Results showed that small (ca. 33 nm) and spherical particles were obtained with positive surface charge (+9.54 mV). Infrared analyses determined that encapsulation of genistein was successfully achieved with an efficiency of 51%; it was observed that encapsulation process enhanced the aqueous dispersibility of genistein and cumulative release of genistein was pH-dependent. More important, after encapsulation data showed that Gen potentiated its antioxidant and antiproliferative effects on HT29 human colon cancer cells by the modulation of endogenous antioxidant enzymes and HO production, which simultaneously activated two different processes of cell death (apoptosis and autophagy), unlike free genistein that only activated one (apoptosis) in a lower proportion. Overall, our data support that Gen-PEG-SiHNM could be potentially used as alternative treatment for colorectal cancer in a near future.
由于染料木黄酮（Gen）的水溶性低、生物利用度低以及在实验条件下不稳定，其抗癌应用受到严重限制。为了克服这些限制，我们提出了一种基于将Gen掺入聚乙二醇化二氧化硅纳米颗粒（PEG-SiNPs）（Gen-PEG-SiHNM）的杂化纳米材料（HNM）配方，并评估了它们对HT29细胞的物理化学和生物学作用。通过简单的末端有效水分散法获得了负载染料木黄酮的聚乙二醇化二氧化硅杂化纳米材料。通过其平均粒径、表面电荷、载药量、光谱性质、释放曲线和水溶性来确定物理化学性质。通过评估其抗氧化能力并阐明其抗增殖机制来进行生物学性能研究。结果表明，获得了小的（约33 nm）球形颗粒，表面带正电荷（+9.54 mV）。红外分析确定染料木黄酮的包封成功实现，效率为51%；观察到包封过程增强了染料木黄酮的水分散性，并且染料木黄酮的累积释放是pH依赖性的。更重要的是，包封后的数据表明，Gen通过调节内源性抗氧化酶和HO的产生，增强了其对HT29人结肠癌细胞的抗氧化和抗增殖作用，同时激活了两种不同的细胞死亡过程（凋亡和自噬），这与游离染料木黄酮不同，游离染料木黄酮仅以较低比例激活一种（凋亡）。总体而言，我们的数据支持Gen-PEG-SiHNM在不久的将来可能被用作结直肠癌的替代治疗方法。
