两种粒径磁性Fe_3O_4纳米粒的肿瘤靶向及光热治疗研究

Research on tumor targeting and photothermal therapy effect of magnetic Fe_3O_4 nanoparticles with different particle sizes

目的利用四氧化三铁(Fe_3O_4)纳米粒作为模型,研究粒径对纳米粒子靶向性的影响,同时考察不同粒径Fe_3O_4的光热治疗效果。方法本研究采用水热法合成50 nm(Fe_3O_4-50)和210 nm(Fe_3O_4-210)两种粒径的Fe_3O_4纳米粒,考察其光热升温效果、细胞摄取情况和各水平磁响应性;评价外磁场介导下纳米粒在荷瘤小鼠中体内分布情况,并开展体内光热治疗。结果所制备的Fe_3O_4纳米粒形貌均一。两种纳米粒在体外具有近似的光热转化效率,近红外光照射5 min后,两组溶液均从25°C升至72°C;Fe_3O_4-50细胞摄取水平较高,对细胞的光热杀伤效果较好,1.5 W·cm^(-2)照射3 min后细胞存活率低于60%,而相同条件下,Fe_3O_4-210的细胞存活率高于75%。体内分布结果显示,Fe_3O_4-210具有更好的肿瘤靶向及治疗效果,照射3 min后,肿瘤部位温度达到47.3℃,而Fe_3O_4-50温度低于40℃。结论两种粒径Fe_3O_4均具有良好的光热效果。小粒径Fe_3O_4(50 nm)具有较高的细胞摄取效果;大粒径Fe_3O_4(210 nm)具有更好的肿瘤靶向能力,更适合于肿瘤热消融治疗。

AIM To study the influence of nanoparticle size on the tumor targeting effect by using iron oxide as model and to investigate the photothermal therapy effect of iron oxide with different particle size.METHODS Fe3O4 nanoparticles with particle size of 50 nm（ Fe3O4-50） and 210 nm（ Fe3O4-210） were synthesized using solvothermal method. The photothermal effect, cellar uptake and magnetic responsiveness were investigated. Besides, the biodistribution of Fe3O4 nanoparticles with an external magnetic field and the photothermal therapeutic effect in vivo were studied. RESULTS The results indicated that the obtained Fe3O4 nanoparticles were uniform and the nanoparticles with different size displayed similar photothermal effect in vitro.After irradiated with near-infrared light for 5 min, the temperature of the two solutions increased from 25 ℃ to72 ℃. Compared to the large nanoparticles, small nanoparticles exhibited greater cellular uptake ability, thus inducing a higher cancer cell inhibition（ with cell viability below 60%） than large nanoparticles（ with cell viability over 75%） after irradiated with for 3 min at a power density of 1.5 W·cm-2. Interestingly, the results of biodistribution demonstrated that Fe3O4-210 nanoparticles had greater tumor targeting and therapeutic effect.After irradiation for 3 min, the temperature of tumor of Fe3O4-210 reached 47.3 ℃ while that of the Fe3O4-50 was below 40 ℃. CONCLUSION Fe3O4 nanoparticles with two different sizes exhibit excellent photothermal effect. Small nanoparticles（ 50 nm） have greater cellar uptake, while large nanoparticles（ 210 nm） show better tumor targeting effect and are more suitable for tumor thermal ablation.