一种MRI可视化介导的Fe_(3)O_(4)复合纳米体系的制备及其在肿瘤光热联合治疗中的应用  

Preparation of Fe_(3)O_(4) composite nanosystem mediated by MRI visualization and its application in tumor photothermal therapy

作　　者：陈郑胜男 任方丽 宏伟 李文婷 CHEN Zhengshengnan;REN Fangli;HONG Wei;LI Wenting(Department of Pharmacy,Binzhou Medical University,Yantai 264003,Shandong,P.R.China)

机构地区：[1]滨州医学院药学院,山东烟台264003

出　　处：《滨州医学院学报》2024年第3期168-174,共7页Journal of Binzhou Medical University

基　　金：国家自然科学基金青年基金(31800837);滨州医学院高层次人才科研启动基金(2019KYQD19)。

摘　　要：目的通过乳化-溶剂挥发法制备新型Fe_(3)O_(4)/780复合纳米粒(Fe/780 NPs),用于指导磁共振成像(MRI)可视化引导下的肿瘤光热联合治疗。方法利用动态光散射仪(DLS)和透射电子显微镜(TEM)测定Fe/780 NPs的粒径分布、微观形貌;采用近红外热成像评价Fe/780 NPs的光热转换效果,通过溶血实验评价Fe/780 NPs的生物相容性,通过检测细胞内活性氧(ROS)水平、细胞活/死双染实验和MTT实验评价体外抗肿瘤活性;采用7.0 T小动物磁共振成像仪分析复合纳米粒在肿瘤部位的MRI成像效果;通过建立4T1肿瘤细胞异位移植瘤模型,考察制剂的体内联合抑瘤效果。结果采用乳化-溶剂挥发法成功制备高效共载IR780和MNPs的递送纳米体系,纳米颗粒粒径分布均一,MNPs的加入使体系的光热转换性能明显优于单一光敏剂,减少了光敏剂用量,使生物毒性降低,并且升温过程更加温和,避免了过高热的产生。在体内外抗肿瘤实验过程中表现出很好的抗肿瘤活性,能够靶向到肿瘤部位并且具有良好的MRI成像能力。结论Fe/780 NPs可用于MRI可视化介导的肿瘤光热联合治疗,使癌症的诊断和治疗更加准确。Objective To investigate the preparation of novel Fe_(3)O_(4)/780 composite nanoparticles(Fe/780 NPs)by emulsification-solvent evaporation method for guiding magnetic resonance imaging(MRI)visualization-guided combined photothermal therapy of tumors.Methods The particle size distribution and morphology of Fe/780 NPs were determined by dynamic light scattering(DLS)and transmission electron microscopy(TEM).Near-infrared thermal imaging was used to evaluate the photothermal conversion effect of Fe/780 NPs.Hemolysis test was used to evaluate the biocompatibility of Fe/780 NPs.The antitumor activity in vitro was evaluated by detecting intracellular reactive oxygen species(ROS),cell alive/dead double staining and MTT assay.A 7.0 T small animal magnetic resonance imaging instrument was used to analyze the MRI imaging effect of the nanoparticles in the tumor sites.The anti-tumor effect of the preparations in vivo was evaluated by establishing a 4T1 tumor cell ectopic transplantation tumor model.Results The highly efficient co-loaded IR780 and MNPs delivery nanosystem was successfully prepared by emulsification-solvent volatilization method,and the nanoparticle size distribution was uniformed.The addition of MNPs made the photothermal conversion performance of the system significantly better than that of the single ones,reducing the dose,enhancing the biological compatibility,and making it a mild heating process to avoid the generation of excessive heat.It showed good anti-tumor activity in vivo and in vitro anti-tumor experiments,which could be targeted to tumor sites and has good MRI imaging ability.Conclusion Fe/780 NPs can be used for MRI visualization mediated photothermal therapy of tumors,which can make the diagnosis and treatment of cancer more accurate.

关 键 词：纳米颗粒 抗肿瘤 光热疗法 磁共振造影剂 

分 类 号：R811.1[医药卫生—放射医学]