Mirzaghavami Parvin Sadat, Khoei Samideh, Khoee Sepideh, Shirvalilou Sakine, Mahdavi Seied Rabi, Pirhajati Mahabadi Vahid
Student Research Committee, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Finetech in medicine research center, Iran University of Medical Sciences, Tehran, Iran; Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Mater Sci Eng C Mater Biol Appl. 2021 May;124:112043. doi: 10.1016/j.msec.2021.112043. Epub 2021 Mar 24.
Normal tissue complication and development of radioresistance in cancer cells are known as the main challenges of ionizing radiation treatment. In the current study, we intended to induce selective radiosensitization in HT29 cancer cells by developing folic acid modified magnetic triblock copolymer nanoparticles as carrier of 5-Flourouracil (5-FU) which was further used in combination with hyperthermia. The aforementioned nanoparticles were synthesized and characterized by differential scanning calorimetric analysis (DSC), UV-visible spectroscopy, dynamic light scattering (DLS), zeta sizer, and transmission electron microscopy (TEM). These nanoparticles were also assessed to determine drug loading capacity (DLC %) and drug release profile. The cytotoxicity of nanoparticles was evaluated on two different cell lines: HUVEC and HT29. Furthermore, radiosensitivity induction of the nanoparticles with and without exposure of alternative magnetic field was investigated. MTT-based cytotoxicity assay demonstrated that the therapeutic ratio was enhanced in response to using 5-FU-loaded nanoparticles as compared to 5-FU. Various characterizations including gene expression study, measurement of reactive oxygen species (ROS) generation, Annexin V/PI staining, and clonogenic assay revealed that ionizing radiation in combination with hyperthermia in the presence of the synthesized nanoparticles led to maximal anti-cancer effects as compared to other single (P < 0.001) and combined treatments (P < 0.01). Our results suggested that combined treatment based on using folic acid modified magnetic copolymer nanoparticle as carrier of 5-FU accompanied with hyperthermia could be proposed as an efficient approach to enhance radiation effects in cancer cells.
正常组织并发症和癌细胞放射抗性的发展是电离辐射治疗的主要挑战。在本研究中，我们旨在通过开发叶酸修饰的磁性三嵌段共聚物纳米颗粒作为5-氟尿嘧啶（5-FU）的载体，在HT29癌细胞中诱导选择性放射增敏，该纳米颗粒进一步与热疗联合使用。通过差示扫描量热分析（DSC）、紫外可见光谱、动态光散射（DLS）、zeta粒度分析仪和透射电子显微镜（TEM）对上述纳米颗粒进行了合成和表征。还对这些纳米颗粒进行了评估，以确定载药量（DLC%）和药物释放曲线。在两种不同的细胞系HUVEC和HT29上评估了纳米颗粒的细胞毒性。此外，研究了在有无交变磁场暴露情况下纳米颗粒的放射敏感性诱导情况。基于MTT的细胞毒性试验表明，与5-FU相比，使用载有5-FU的纳米颗粒可提高治疗比率。包括基因表达研究、活性氧（ROS）生成测量、Annexin V/PI染色和克隆形成试验在内的各种表征表明，与其他单一治疗（P<0.001）和联合治疗（P<0.01）相比，在合成纳米颗粒存在的情况下，电离辐射与热疗联合使用可产生最大的抗癌效果。我们的结果表明，基于使用叶酸修饰的磁性共聚物纳米颗粒作为5-FU载体并伴有热疗的联合治疗可被提议作为一种增强癌细胞辐射效应的有效方法。
