改性载顺铂磁性纳米药物靶向治疗鼻咽癌的实验研究

Experimental study of therapy effect of CDDP-loaded magnetic nanoparticles targeting for nasopharyngeal carcinoma

目的研究改性载顺铂磁性纳米药物(CDDP-MNP)靶向治疗鼻咽癌的疗效。方法分别以浓度不同的载顺铂磁性纳米药物作用于体外培养的CNE-2细胞不同的时间,并以单纯顺铂做对照,用MTT方法定量检测CNE-2细胞在2种药物处理前后细胞凋亡的情况。同步进行体外抑瘤实验,将20只BALB/c雌性裸鼠接种CNE-2细胞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、改性载顺铂磁性纳米药物治疗组、改性载顺铂磁性纳米药物联合靶向治疗组,分别用相应药物干预。治疗前后称体重、测量肿瘤大小、处死后称量瘤体重量,同时取移植瘤组织进行病理检查。结果改性载顺铂磁性纳米药物对CNE2细胞的杀伤作用呈明显量效和时效关系,与顺铂比较差异无显著性(P>0.05)。在体内抑瘤实验中,给予顺铂及改性载顺铂磁性纳米药物治疗后,裸鼠体重明显减轻,肿瘤增长明显减慢。改性载顺铂磁性纳米药物治疗组与顺铂治疗组疗效比较差异无显著性(P>0.05);但改性载顺铂磁性纳米药物联合磁靶向治疗组,鼻咽癌裸鼠移植瘤的抑瘤率明显高于顺铂治疗组及改性载顺铂磁性纳米药物治疗组(P<0.05)。结论改性载顺铂磁性纳米药物联合磁靶向治疗鼻咽癌有良好的疗效。

[Objective] In order to explore the therapeutic effect of Cis-Diammine-Dichloroplatium （CDDP） loaded magnetic nanopartieles（MNP） targeting for nasopharyngeal carcinoma. [Methods] CNE-2 cell line was treated with CDDP-MNP with different concentration and time and CDDP was used as control agent. The apoptosis of CNE-2 cell line treated with CDDP-MNP or CDDP were detected by MTT method. At the same time, The inhibitory experiment of tumor grouth in vivo were carried out in nude rats with transplanted tumors of CNE-2 cell. Twenty BALB/c female rats with implanted tumor of CNE-2 cells were randomly divided into implanting tumor controlling group, treating group with CDDP, treating group with CDDP-MNP and treating group with CDDP-MNP combining outside magnetic field. The animal of each group was intervened with 0.2 mL normal saline or corresponding drugs （equal to 2 mg CCDP） respectively. Before and after the treatment, the weight of rat, the volume and the weight of the transplanting tumor were measured. The tissues of transplanting tumor were detected by routine pathological method. [Results] The kill and wound rate of CDDP-MNP to CNE-2 cell in vitro presented an obvious dose-effect and time-effect relation, but there was not a significant difference （P 〉0.05） comparing with CCDP. As seen in the experiments in vivo, the weight of rat significantly decreased and the growth of the transplanting tumor was obviously slowed in treating groups. There was no significant difference between treating group with CDDP and treating group with CDDP-SAMNP （P〉0.05）. However, the growth inhibitory rate of transplanted tumor significantly increased in treating group with CDDP-SAMNP combined with outside magnetic field than in the other treating groups （P 〈0.05）. [Conclusion] The targeting therapy of CDDP-MNP combining with outside magnetic field can effectively inhibit the growth of nasopharyngeal carcinoma of nude mouse.