GEIMM, Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
GEIMM, Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianópolis, SC, Brazil; PGMAT, Department of Mechanical Engineering, Federal University of Santa Catarina, Florianópolis, SC, Brazil.
Mater Sci Eng C Mater Biol Appl. 2020 Apr;109:110555. doi: 10.1016/j.msec.2019.110555. Epub 2019 Dec 14.
Breast cancer is a major cause of death among women worldwide. Resistance to conventional therapies has been observed in HER2-positive breast cancer patients, indicating the need for more effective treatments. Small interfering RNA (siRNA) therapy is an attractive strategy against HER2-positive tumors, but its success depends largely on the efficient delivery of agents to target tissues. In this study, we prepared a magnetic hybrid nanostructure composed of iron oxide nanoparticles coated with caffeic acid and stabilized by layers of calcium phosphate and PEG-polyanion block copolymer for incorporation of siRNA. Transmission electron microscopy images showed monodisperse, neutrally charged compact spheres sized <100 nm. Dynamic light scattering and nanoparticle tracking analysis revealed that the nanostructure had an average hydrodynamic diameter of 130 nm. Nanoparticle suspensions remained stable over 42 days of storage at 4 and 25 °C. Unloaded caffeic acid-magnetic calcium phosphate (Caf-MCaP) nanoparticles were not cytotoxic, and loaded nanoparticles were successfully taken up by the HER2-positive breast cancer cell line HCC1954, even more so under magnetic guidance. Nanoparticles escaped endosomal degradation and delivered siRNA into the cytoplasm, inducing HER2 gene silencing.
乳腺癌是全球女性死亡的主要原因之一。HER2 阳性乳腺癌患者对常规治疗产生耐药性，表明需要更有效的治疗方法。小干扰 RNA（siRNA）治疗是针对 HER2 阳性肿瘤的一种有吸引力的策略，但它的成功在很大程度上取决于将药物有效递送到靶组织。在这项研究中，我们制备了一种由氧化铁纳米粒子组成的磁性杂化纳米结构，这些纳米粒子被咖啡酸包覆，并由磷酸钙层和聚乙二醇-聚阴离子嵌段共聚物稳定，用于掺入 siRNA。透射电子显微镜图像显示出单分散的、带中性电荷的、小于 100nm 的紧凑球体。动态光散射和纳米颗粒跟踪分析表明，该纳米结构的平均水动力直径为 130nm。纳米颗粒悬浮液在 4°C 和 25°C 下储存 42 天仍保持稳定。未负载的咖啡酸-磁性磷酸钙（Caf-MCaP）纳米颗粒没有细胞毒性，负载的纳米颗粒被 HER2 阳性乳腺癌细胞系 HCC1954 成功摄取，在磁场引导下摄取更多。纳米颗粒逃脱了内体降解，并将 siRNA 递送到细胞质中，诱导 HER2 基因沉默。
