基于癌细胞膜修饰的氧化铁组装体构建化学动力肿瘤治疗体系

Iron oxide assembly with unique morphology and proper modification may achieve excellent anti-tumor performance. In this project, iron oxide assemblies with different morphologies、degradable silica and cancer cell membrane will be combined to fabricate chemodynamic reagent. We try to investigate the relationship between morphologies、surface modification of assembly and the performances of the chemodynamic reagent. Firstly, iron oxide assemblies with tailored morphologies will be synthesized. Then, degradable silica will be controlled modified on the surface of the assembly. Cancer cell membrane will be wrapped on the surface of silica to obtain composite nanoparticles. Fenton reaction ability and photothermal performance of iron oxide will be explored to achieve efficient chemodynamic treatment; Degradable silica will reduce the resistance of chemodynamic treatment by consuming glutathione; Iron oxide can used for magnetic targeting and magnetic resonance imaging while cancer cell membrane can adopt to homologous targeting. Finally, chemodynamic reagent with high efficiency, dual targeting function and magnetic resonance imaging ability will be fabricated and screened. This project will promote the combination of material sciences with oncology and accelerate the development of high-efficiency tumor diagnosis and treatment reagents. Moreover, the chemodynamic reagent obtained using this strategy may be of practical significance for tumor diagnosis and treatment.

氧化铁组装体独特的形貌及适当的修饰可能赋予其优异的抗肿瘤性能。本项目通过将不同形貌的氧化铁组装体与可降解氧化硅、癌细胞膜复合构建化学动力治疗试剂，力图研究组装体的形貌、表面修饰等因素对其作为化学动力治疗试剂的影响。首先设计合成多种形貌氧化铁组装体，将可降解氧化硅可控修饰在组装体表面，通过挤出方法将癌细胞膜包裹在氧化硅外层得到复合纳米颗粒。利用氧化铁可发生芬顿反应的能力和光热性能实现高效的化学动力治疗；利用可降解氧化硅消耗谷胱甘肽的能力降低化学动力学治疗的阻力；利用氧化铁的磁靶向和癌细胞膜的同源靶向作用及氧化铁的核磁成像能力，最终构建并筛选出具有核磁成像能力、双重靶向性、高效的化学动力治疗试剂。本研究推进了材料学与肿瘤学的有机结合，加速高效肿瘤诊疗试剂的开发。更重要的是，通过这种方式设计的化学动力试剂可能对肿瘤诊疗具有现实意义。

氧化铁纳米组装体可作为肿瘤治疗试剂用于化学动力治疗。但是单一的化学动力治疗效果有限，通过对氧化铁组装体的形貌组分进行调控，并对表面进行适当的修饰可赋予更加优异的抗肿瘤性能。本项目设计合成了多种组分的氧化铁基组装体并对其表面进行靶向修饰用于光热促进的肿瘤化学动力治疗、免疫治疗以及核磁成像。实验结果表明，该治疗体系可以使纳米颗粒高效靶向递送到肿瘤部位，促进了纳米颗粒在肿瘤部位的富集，有效抑制了肿瘤的发生及发展。此外，氧化铁的核磁成像功能使治疗体系实现了成像引导的精准治疗。本研究成功构建并筛选出具有核磁成像能力、多重靶向性、高效的肿瘤治疗试剂，并对其治疗机制进行了深入研究。本项目推进了材料学与肿瘤学的有机结合，对肿瘤诊疗试剂的研发具有现实意义。