磁性普鲁士蓝介导光热消融肿瘤及三模态成像研究

Tri-modal Imaging Mediated Theranostic Magnetic Prussian Blue Nanoparticles for Photothermal Tumor Ablation

目的制备具有近红外光响应光热转换特性的磁性中空普鲁士蓝纳米颗粒(HMNP-PBNPs),综合考察其在近红外激光辐照下对Hep G2肝癌细胞的光热消融治疗效果。材料与方法采用聚苯乙烯微球模板法制备中空磁性纳米颗粒(HMNP),然后利用共沉淀法在其表面包覆具有近红外光强吸收的普鲁士蓝(PBNPs)纳米外壳制成HMNP-PBNPs。对其形态结构、粒径分布、磁学性能,及其在近红外激光(808 nm,5 min,1.2 W/cm^2)辐照下产热性能和对肿瘤的光热消融疗效进行表征和验证;同时采用多模态体外成像研究考察HMNP-PBNPs的MRI、红外热成像(ITI)及光声成像(PAI)的体外成像性能。结果 HMNP-PBNPs呈规则的"核-壳"结构形态、分散性良好、其粒径大小约为(131.7±11.6)nm,壳层厚度约为18.5 nm;颗粒具有良好的磁学性能(36.6emu/g)和光热转换性能(>50℃),在808 nm近红外激光辐照下能有效杀伤肿瘤细胞(>80%)。体外成像检测结果显示:与双蒸水对照组比较,200μg/ml HMNP-PBNPs的MRI信号值(q=16.5,P<0.05)、PAI信号值(q=8.2,P<0.05)及ITI信号强度增加,体现出良好的MRI/PAI/ITI多模态成像性能。结论本研究成功设计制备了一种三模态成像介导的诊断治疗一体化的近红外光响应肿瘤光热消融诊疗剂HMNP-PBNPs,具有潜在的临床应用价值。

Purpose To prepare hollow magnetic nanoparticle-Prussian blue nanoparticles(NMNP-PBNPs)with photothermal conversion characteristics responding to near infrared(NIR),and to evaluate its photothermal ablation effect on HepG2 cell by irradiating with NIR.Materials and Methods The hollow magnetic nanoparticle(HMNP)were prepared by polystyrene template method,and then Prussian Blue(PB)nanoshells were coated on the surfaces of HMNP by coprecipitating to produce HMNP-PBNPs.Next,the morphology,particle size distribution,magnetic property,thermogenesis property and photothermal cytotoxicity to tumor cells under NIR laser irradiation(808 nm,5 min,1.2 W/cm2)of HMNP-PBNPs were investigated in this study.The multimodal in vitro imaging characteristics were measured with MRI,photoacoustic imaging(PAI)and infrared thermal imaging(ITI).Results HMNP-PBNPs presented regular“core-shell”morphology with well dispersity,average diameter of 131.7±11.6 nm and shell thicknesses of about 18.5 nm.The particles had good magnetic properties(36.6 emu/g)and photothermal conversion performance(>50℃),which could effectively kill tumor cells(>80%)under near-infrared laser irradiation at 808 nm.The results of in vitro imaging showed that the MRI signal values(q=16.5,P<0.05),PAI signal values(q=8.2,P<0.05)and enhanced ITI signals of 200μg/ml HMNP-PBNPs exhibited more excellent MRI/PAI/ITI multimodal imaging performance than those in double-distilled water control group.Conclusion Tri-modal imaging mediated theranostic HMNP-PBNPs are successfully prepared for NIR laser induced photothermal tumor ablation,which are of potential value in clinical application.