Calero Macarena, Chiappi Michele, Lazaro-Carrillo Ana, Rodríguez María José, Chichón Francisco Javier, Crosbie-Staunton Kieran, Prina-Mello Adriele, Volkov Yuri, Villanueva Angeles, Carrascosa José L
Departamento de Biología, Universidad Autónoma de Madrid, Cantoblanco, 28049, Madrid, Spain.
Instituto Madrileño de Estudios Avanzados en Nanociencia (IMDEA Nanociencia), Cantoblanco, 28049, Madrid, Spain.
J Nanobiotechnology. 2015 Feb 26;13:16. doi: 10.1186/s12951-015-0073-9.
Different superparamagnetic iron oxide nanoparticles have been tested for their potential use in cancer treatment, as they enter into cells with high effectiveness, do not induce cytotoxicity, and are retained for relatively long periods of time inside the cells. We have analyzed the interaction, internalization and biocompatibility of dimercaptosuccinic acid-coated superparamagnetic iron oxide nanoparticles with an average diameter of 15 nm and negative surface charge in MCF-7 breast cancer cells.
Cells were incubated with dimercaptosuccinic acid-coated superparamagnetic iron oxide nanoparticles for different time intervals, ranging from 0.5 to 72 h. These nanoparticles showed efficient internalization and relatively slow clearance. Time-dependent uptake studies demonstrated the maximum accumulation of dimercaptosuccinic acid-coated superparamagnetic iron oxide nanoparticles after 24 h of incubation, and afterwards they were slowly removed from cells. Superparamagnetic iron oxide nanoparticles were internalized by energy dependent endocytosis and localized in endosomes. Transmission electron microscopy studies showed macropinocytosis uptake and clathrin-mediated internalization depending on the nanoparticles aggregate size. MCF-7 cells accumulated these nanoparticles without any significant effect on cell morphology, cytoskeleton organization, cell cycle distribution, reactive oxygen species generation and cell viability, showing a similar behavior to untreated control cells.
All these findings indicate that dimercaptosuccinic acid-coated superparamagnetic iron oxide nanoparticles have excellent properties in terms of efficiency and biocompatibility for application to target breast cancer cells.
不同的超顺磁性氧化铁纳米颗粒已被测试其在癌症治疗中的潜在用途,因为它们能高效进入细胞,不诱导细胞毒性,且能在细胞内保留相对较长时间。我们分析了平均直径为15 nm且表面带负电荷的二巯基琥珀酸包被的超顺磁性氧化铁纳米颗粒与MCF-7乳腺癌细胞的相互作用、内化及生物相容性。
将二巯基琥珀酸包被的超顺磁性氧化铁纳米颗粒与细胞孵育不同时间间隔,从0.5小时到72小时。这些纳米颗粒显示出高效内化和相对缓慢的清除。时间依赖性摄取研究表明,孵育24小时后二巯基琥珀酸包被的超顺磁性氧化铁纳米颗粒积累量最大,之后它们从细胞中缓慢清除。超顺磁性氧化铁纳米颗粒通过能量依赖的内吞作用内化并定位在内体中。透射电子显微镜研究表明,根据纳米颗粒聚集体大小,存在巨胞饮摄取和网格蛋白介导的内化。MCF-7细胞积累这些纳米颗粒,对细胞形态、细胞骨架组织、细胞周期分布、活性氧生成和细胞活力没有任何显著影响,表现出与未处理对照细胞相似的行为。
所有这些发现表明,二巯基琥珀酸包被的超顺磁性氧化铁纳米颗粒在靶向乳腺癌细胞应用方面在效率和生物相容性方面具有优异特性。