铁原子簇掺杂氧化铁靶向纳米磁热疗剂的构建及其乳腺癌转移瘤疗效评价

Magnetic nanomaterials have revolutionized the biomedical arena, particularly, superparamagnetic iron oxide nanoparticles (SPIOs). However, to enhance the efficacy of this material we need to overcome the intrinsic drawbacks of SPIOs i.e. smaller size, weaker magnetic properties, and lower magnetic hyperthermia performance during cancer cells treatment. The idea is to enhance the magnetic and associated theranostic parameters of magnetic material. Herein, we propose to construct an innovative iron-clusters doped iron oxide nanoparticles as magnetic hyperthermia agent with optimum biocompatibility, higher saturation magnetization suitable to enhance the magnetic heating conversion efficiency. After coupling with targeting molecule CREKA, iron-clusters doped iron oxide nanoparticles are expected to deliver therapeutics and show high-performance activity against triple negative breast cancer metastases. The key control parameters for the fabrication of iron-clusters doped iron oxide nanoparticles will be investigated to optimize the effect of size, composition as well as the magnetic properties for developing an improved magnetic hyperthermia modality. The mechanism of magnetic hyperthermia treatment on cancer metastases based on iron-clusters doped iron oxide nanoparticles would be deducted, and the same idea would be utilized in the therapy of triple-negative breast cancer metastases. The results obtained from this study will not only provide a general strategy to construct a variety of highly efficient magnetic hyperthermia agent but also provide a new choice for the magnetic hyperthermia treatment of triple-negative breast cancer metastases and overcome the drawbacks of SPIOs in the future.

针对当前占主导地位的小尺寸超顺磁纳米氧化铁纳米颗粒低的磁学性能和磁热效率导致以其开发的肿瘤纳米磁热疗剂远不能满足临床肿瘤治疗需求的问题，本项目提出具有良好生物安全性、小尺寸、高磁学性能和磁热效率的铁原子簇掺杂氧化铁纳米颗粒，偶联靶向分子CREKA（Cys-Arg-Glu-Lys-Ala），构建新型、高效的靶向纳米磁热疗剂用于三阴乳腺癌转移瘤治疗。研究基于铁原子簇掺杂氧化铁靶向纳米磁热疗剂的关键制备控制因素以及尺寸、组分、磁学性能与磁热疗疗效之间的构效关系；揭示基于铁原子簇掺杂氧化铁靶向纳米磁热疗剂的靶向转移瘤磁热疗机制并初步确立其在三阴乳腺癌转移瘤磁热疗优势。本项目以新型铁原子簇掺杂的氧化铁纳米颗粒平台构建的靶向纳米磁热疗剂为模型展开基础研究，研究结果可为高效靶向纳米磁热疗剂的构建提供理论和方法基础，为基于纳米磁热疗剂的三阴乳腺癌转移瘤的综合治疗提供一个新的选择。

针对当前占主导地位的小尺寸超顺磁纳米氧化铁纳米颗粒低的磁学性能和磁热效率导致以其开发的肿瘤纳米磁热疗剂远不能满足临床肿瘤治疗需求的问题，本项目提出了具有良好生物安全性、小尺寸、高磁学性能和磁热效率的铁原子簇掺杂氧化铁纳米颗粒，偶联靶向分子CREKA（Cys-Arg-Glu-Lys-Ala），构建了新型、高效的靶向纳米磁热疗剂用于三阴乳腺癌转移瘤治疗。研究了基于铁原子簇掺杂氧化铁靶向纳米磁热疗剂的关键制备控制因素以及尺寸、组分、磁学性能与磁热疗疗效之间的构效关系；揭示了基于铁原子簇掺杂氧化铁靶向纳米磁热疗剂的靶向肿瘤磁热疗机制并初步确立其在三阴乳腺癌磁热疗优势。本项目以新型铁原子簇掺杂的氧化铁纳米颗粒平台构建的靶向纳米磁热疗剂为模型展开基础研究，研究结果可为高效靶向纳米磁热疗剂的构建提供理论和方法基础，为基于纳米磁热疗剂的三阴乳腺癌的综合治疗提供一个新的选择。