Lin Hailei, Yin Liangliang, Chen Beidong, Ji Yanqin
Key Laboratory of Radiological Protection and Nuclear Emergency, China CDC, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing 100088, China.
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, China.
Colloids Surf B Biointerfaces. 2022 Nov;219:112814. doi: 10.1016/j.colsurfb.2022.112814. Epub 2022 Aug 30.
Nanomaterials in particular the magnetic nanoparticles (MNPs) offer tremendous potential for cancer treatment due to their unique intrinsic properties. Combining materials with a variety of functional groups, and forming a multifunctional nanosystem to overcome the limitations of monotherapy for cancer treatment has always been a research focus with notable difficulties. Considering the many challenges faced by radiotherapy and hyperthermia, in this study, we designed a rational strategy for magnetic hyperthermia using FeO@SiO@Sec2@FA nanoparticles as a novel nano-radiosensitizer to simultaneously enhance the therapeutic effects of radiotherapy in the future. FeO@SiO core-shell structured nanoparticles were synthesized with an appropriate silica layer thickness to maintain good saturation magnetization. The as-prepared FeO@SiO@Sec2@FA nanoparticles had the specific absorption rate (SAR)value of 57 W/g, which was below the clinically acceptable alternating magnetic field value of 4.9 × 10 Ams, indicating good heat generation efficiency (the temperature level ΔT=6-10 °C). Moreover, Folate-modified nanoparticles exhibited approximately 6-fold higher cellular internalization of Hela cells with no obvious cytotoxicity for the Hela and MDA-MB-231 cells, and lower cytotoxicity for the HUVECs in a concentration range of 0-150 µg/mL. In addition, these nanoparticles were modified on the silica surface by L-selenocystine, which could enhance the elimination of tumor cells by producing reactive oxygen species under X-rays, resulting in a novel radiosensitization effect. Therefore, the as-prepared FeO@SiO@Sec2@FA nanoparticles with good biocompatibility and active targeting would possess synergistic magnetic hyperthermia/radiotherapy effect.
纳米材料尤其是磁性纳米颗粒(MNPs)因其独特的内在特性在癌症治疗方面具有巨大潜力。将具有多种官能团的材料结合起来,形成多功能纳米系统以克服癌症单药治疗的局限性,一直是研究重点且存在显著困难。考虑到放射治疗和热疗面临的诸多挑战,在本研究中,我们设计了一种合理的策略,使用FeO@SiO@Sec2@FA纳米颗粒作为新型纳米放射增敏剂进行磁热疗,以期在未来同时增强放射治疗的效果。合成了具有适当二氧化硅层厚度的FeO@SiO核壳结构纳米颗粒,以保持良好的饱和磁化强度。所制备的FeO@SiO@Sec2@FA纳米颗粒的比吸收率(SAR)值为57W/g,低于临床可接受的4.9×10A/m的交变磁场值,表明具有良好的发热效率(温度升高ΔT = 6 - 10°C)。此外,叶酸修饰的纳米颗粒对Hela细胞的细胞内化作用比未修饰的高约6倍,在0 - 150μg/mL浓度范围内对Hela和MDA - MB - 231细胞无明显细胞毒性,对人脐静脉内皮细胞(HUVECs)的细胞毒性较低。另外,这些纳米颗粒通过L - 硒代胱氨酸在二氧化硅表面进行了修饰,其在X射线照射下可通过产生活性氧增强肿瘤细胞的清除,从而产生一种新型的放射增敏效应。因此,所制备的具有良好生物相容性和主动靶向性的FeO@SiO@Sec2@FA纳米颗粒将具有协同磁热疗/放射治疗效果。