载顺铂磁性纳米药物在鼻咽癌裸鼠移植瘤组织内的分布及靶向性研究

An Experimental Study of the Distribution and Targeting Effect of CDDP-loaded Magnetic Nanoparticles in Nude Mice with Transplanted Nasopharyngeal Carcinoma

目的研究载顺铂磁性纳米药物(CDDP-MNP)在鼻咽癌裸鼠移植瘤组织内的靶向性分布。方法将20只BALB/c雌性裸鼠接种人鼻咽癌细胞CNE-2建立鼻咽癌裸鼠移植瘤模型,按照肿瘤体积随机分成单纯移植瘤对照组、顺铂治疗组、载顺铂磁性纳米药物治疗组、载顺铂磁性纳米药物联合靶向治疗组,分别用生理盐水及相应药物干预。最后一次用药后第3天行裸鼠MR活体检测,MR检测后处死裸鼠,取下肿瘤,分别进行电镜检测、原子吸收光谱和铁染色检测。结果 MR显示,载顺铂磁性纳米药物联合磁靶向治疗组与其他3个组比较,在T2W I时相肿瘤组织的信号明显降低。电镜检查在3个治疗组均可见肿瘤组织大片坏死,在载顺铂磁性纳米药物联合磁靶向治疗组肿瘤细胞胞质中可见大量纳米颗粒。应用石墨炉原子吸收光谱法在3个治疗组肿瘤组织均可检测到铂,其中载顺铂磁性纳米药物联合磁靶向治疗组铂含量最高,明显高于其他两个治疗组(P<0.05)。铁染色检测载顺铂磁性纳米药物联合磁靶向治疗组肿瘤组织普鲁士染色呈弱阳性,其余3个组呈阴性。结论载顺铂磁性纳米药物在体外磁场的引导下能聚集于肿瘤组织,发挥良好的抗肿瘤生物学效应。

Objective To evaluate the targeted distribution of cis-platin loaded magnetic nanoparticles（CDDP-MNP） in tumor tissue of nude mice with nasopharyngeal carcinoma.Methods Twenty BALB/c female mice with implanted tumor of CNE-2 cells were randomly divided into implanting tumor control group,treating group with CDDP,treating group with CDDP-MNP and treating group with CDDP-MNP combining outside magnetic field（target group）.The animals in each group were given 0.2 ml normal saline or corresponding drugs（equal to 0.1 mg CCDP） by intravenous,total for two times interval three days.Three days after the second administration of medicine,one mice of each group selected at random was examined on MRI T1WI and T2WI,and then all mouse were sacrificed.The transplanting tumor tissue was detected by electro-microscopy,atomic-absorption spectrometry and ferric staining.Results On T2WI,the signal intensity of tumor tissue in target group was significantly lower than that of the other 3 groups.At the same time,tumor cell necrosis was observed under electro microscopy in every therapy groups and the nanoparticles were detected in the tumor cell only in target group.By graphite furnace atomic-absorption spectrometry analysis,platinum in tumor tissue was significantly increased in target group than in the other treating groups（P0.05）.By ferric staining,the weakly positive staining was observed in the tumor cell of target group,and negative in other three groups.Conclusion Under the introduction of the outer magnetic field,the modified magnetic nanoparticles loaded CDDP could be collected within the targeting tumor and efficiently exert its antitumor effect.