Department of Medical Physics and Imaging, School of Allied Medical Sciences, Urmia University of Medical Sciences, Urmia, 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.
Life Sci. 2022 Oct 1;306:120729. doi: 10.1016/j.lfs.2022.120729. Epub 2022 Jun 24.
Recently, the development of new strategies in the treatment and diagnosis of cancer cells such as thermo-radiation-sensitizer and theranostic agents have received a great deal of attention. In this work, folic acid-conjugated temozolomide-loaded SPION@PEG-PBA-PEG nanoparticles (TMZ-MNP-FA NPs) were proposed for use as magnetic resonance imaging (MRI) contrast agents and to enhance the cytotoxic effects of hyperthermia and radiotherapy.
Nanoparticles were synthesized by the Nano-precipitation method and their characteristics were determined by dynamic light scattering (DLS), scanning electron microscopy (SEM) and X-ray powder diffraction (XRD). To evaluate the thermo-radio-sensitization effects of NPs, C6 cells were treated with nanoparticles for 24 h and then exposed to 6-MV X-ray radiation. After radiotherapy, the cells were subjected to an alternating magnetic field (AMF) hyperthermia. The therapeutic potential was assessed using clonogenic assay, ROS generation measurement, flow cytometry assay, and qRT-PCR analysis. Also, the diagnostic properties of the nanoparticles were assessed by MRI.
MRI scanning indicated that nanoparticles accumulated in C6 cells could be tracked by T2-weighted MR imaging. Colony formation assay proved that TMZ-MNP-FA NPs enhanced the anti-proliferation effects of AMF by 1.94-fold compared to AMF alone (P < 0.0001). Moreover, these NPs improved the radiation effects with a dose enhancement factor of 1.65. All results showed that the combination of carrier-based chemotherapy with hyperthermia and radiotherapy caused a higher anticancer efficacy than single- or two-modality treatments.
The nanoparticles advanced in this study can be proposed as the promising theranostic and thermo-radio-sensitizer platform for the diagnosis and tri-modal synergistic cancer therapy.
最近，人们对癌症细胞治疗和诊断的新策略（如热辐射增敏剂和治疗诊断剂）的发展给予了极大关注。在这项工作中，叶酸偶联替莫唑胺负载的 SPION@PEG-PBA-PEG 纳米粒子（TMZ-MNP-FA NPs）被提出用作磁共振成像（MRI）对比剂，并增强热疗和放疗的细胞毒性作用。
通过纳米沉淀法合成纳米粒子，并通过动态光散射（DLS）、扫描电子显微镜（SEM）和 X 射线粉末衍射（XRD）来确定其特性。为了评估 NPs 的热放射增敏作用，将 C6 细胞用纳米粒子处理 24 小时，然后用 6-MV X 射线辐射。放疗后，细胞接受交变磁场（AMF）热疗。采用集落形成实验、ROS 生成测量、流式细胞术分析和 qRT-PCR 分析评估治疗潜力。此外，通过 MRI 评估纳米粒子的诊断特性。
MRI 扫描表明，C6 细胞中积累的纳米粒子可通过 T2 加权磁共振成像进行跟踪。集落形成实验证明，与单独的 AMF 相比，TMZ-MNP-FA NPs 使 AMF 的抗增殖作用增强了 1.94 倍（P<0.0001）。此外，这些 NPs 使辐射效应提高了 1.65 倍。所有结果表明，与单一或两种模式治疗相比，基于载体的化疗与热疗和放疗相结合可产生更高的抗癌疗效。
本研究中提出的纳米粒子可作为有前途的治疗诊断和三模态协同癌症治疗的治疗诊断和热放射增敏剂平台。
