光敏剂-磁性纳米粒子螯合剂对磁性纳米粒子在VX2肝转移癌细胞内靶向性分布的影响

Targeted distribution of photosensitizer-manoparticle conjugates in transplanted VX-2 liver tumors in rabbits

目的:研究光敏剂-磁性纳米粒子螯合物促进磁性纳米粒子在VX2肝转移癌细胞内的靶向性分布.方法:取健康新西兰大白兔40只,体质量2.5-3.0kg.建立VX2肝转移癌模型,随机分成空白对照组、光敏剂组、磁性纳米粒子组和光敏剂-磁性纳米粒子螯合物组,在成瘤后的第16、18和20d,经兔耳缘静脉分别注射生理盐水、光敏剂、磁性纳米粒子和螯合物.于第22d处死试验兔,剖腹观察肿瘤生长情况,取正常肝组织和癌结节,作普鲁氏蓝铁染色、透射电镜检查和原子光谱吸收半定量检测.结果:(1)普鲁氏蓝染色后,在螯合剂组癌结节内见到大量蓝染铁颗粒,明显多于其他各组,而肝细胞内少见蓝染铁颗粒;(2)电镜检查,螯合剂组癌细胞内有大量散在的黑色细小颗粒,主要分布在溶酶体、内质网、线粒体和细胞核内;而肝细胞内只有少量黑色细小颗粒;(3)原子光谱吸收半定量检测显示,在癌结节内,螯合剂组铁含量(9.09mg/L)明显高于空白对照组、光敏剂组和磁性纳米粒子组(P<0.01),癌组织内铁含量也明显高于正常肝组织的铁含量(P<0.01).结论:光敏剂-磁性纳米粒子螯合剂能够促进磁性纳米粒子在肝转移癌结节内的聚集.

AIM： To investigate the targeted distribution of photosensitizer-manoparticle conjugates in transplanted VX-2 liver tumors in rabbits. METHODS： Forty healthy New Zealand rabbits were randomly divided into four groups： normal control group, photosensitizer group, nanoparticle group, and conjugate group. A rabbit model of transplanted VX-2 liver tumor was created. On days 16, 18 and 20 after model creation, the animals in each group were injected with saline, photosensitizer, nanoparticles and conjugate solution via the ear vein, respectively. On day 22, animals were sacrificed to observe the growth of tumors and examine pathological changes in liver tissue by Prussian blue staining, transmission electron microscopy and atomic absorption spectroscopy. RESULTS： Prussian blue staining showed that there were plenty of iron particles stained blue inside cancer cells in the conjugate group, which were much more than those in other groups. There were few iron particles inside normal liver cells. Transmission electron microscopy revealed that there were large quantity of black small particles inside the lysosomes, endoplasmic reticulum, mitochondria and nucleus of cancer cells in the conjugate group, which were much more than those in other groups. There were only few black small particles inside normal liver cells. CONCLUSION： Photosensitizer-nanoparticle conjugates have cancer-targeted effect and could help nanoparticles enter into transplanted VX-2 liver tumor cells.