FA-CM-β-CD-CDDP纳米药物对鼻咽癌的体内靶向治疗研究

Targeted Treatment of Nasopharyngeal Carcinoma with FA-CM-β-CD-CDDP Nanomedicine

目的探讨叶酸(folic acid,FA)分子靶向载顺铂(cisplatin,CDDP)羧甲基-β-环糊精(carboxymethyl-β-cyclodextrin,CM-β-CD)纳米药物(FA-CM-β-CD-CDDP)对鼻咽癌(nasopharyngeal carcinoma,NPC)的体内靶向治疗效应。方法荷叶酸受体(folate receptor,FR)表达阳性的HNE-1瘤和FR表达阴性的CNE-2瘤的同一裸鼠经尾静脉给予FA-CM-β-CD-CDDP纳米药物(按CDDP 10mg·kg-1给药)1.5h后,采用原子吸收光谱法检测2种瘤块组织内的CDDP浓度,分析FA-CM-β-CD-CDDP的体内靶向能力。将20只荷HNE-1瘤裸鼠按随机数字表法分为4组(每组5只),均经尾静脉注射给药0.2mL:对照组注射生理盐水,载体组注射FA-CM-β-CD溶液,CDDP组注射浓度为3mg·kg-1的CDDP溶液,纳米药物组注射FA-CM-β-CD-CDDP溶液(含CDDP浓度3mg·kg-1),给药后21d测量各组HNE-1瘤块体积和质量,并采用免疫组化检测瘤块增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)表达,分析FA-CM-β-CD-CDDP的体内肿瘤抑制效应。结果 HNE-1肿瘤组织内CDDP含量明显高于CNE-2肿瘤组织(P<0.05)。纳米药物组的HNE-1瘤块体积和质量抑瘤率分别为43.36%、41.67%,较载体组(7.91%、5.56%)和CDDP组(24.51%、22.22%)均明显增加;且HNE-1瘤块PCNA阳性细胞指数为47.75%,表达较对照组(90.83%)、载体组(89.62%)和CDDP组(68.43%)均明显降低。结论构建的FA-CM-β-CD-CDDP纳米药物能够靶向抑制FR阳性的NPC瘤块生长。

Objective To investigate the effect of folic acid（FA）-targeted cisplatin（CDDP）con-jugated carboxymethyl-β-cyclodextrin（CM-β-CD）nanomedicine（FA-CM-β-CD-CDDP）on naso-pharyngeal carcinoma（NPC）in vivo.Methods Nude mice bearing folate receptor（FR）-positive HNE-1 tumor and FR-negative CNE-2 tumor were given FA-CM-β-CD-CDDP nanomedicine（CD-DP 10 mg·kg-1 ）via tail vein injection.The concentrations of CDDP in tumor tissues were deter-mined 1.5 hours after injection by using atomic absorption spectroscopy to analyze the targeting ability of FA-CM-β-CD-CDDP.Twenty nude mice bearing HNE-1 tumor were randomly given normal saline（control group,n=5）,FA-CM-β-CD solution（vector group,n=5）,3 mg·kg-1 CD-DP solution（CDDP group,n=5）or 3 mg/kg FA-CM-β-CD-CDDP solution（nanomedicine group, n=5）at a volume of 2 ml via tail vein injection.HNE-1 tumor volume and weight were measured 21 days after administration.Furthermore,the expression of proliferating cell nuclear antigen（PC-NA）was detected by immunohistochemistry to analyze the efficacy of FA-CM-β-CD-CDDP for tumor suppression.Results The concentration of CDDP in HNE-1 tumor was significantly higher than that in CNE-2 tumor（P《0.05）.The inhibition rates of HNE-1 tumor volume and weight in nanomedicine group（43.36% and 41.67%,respectively）were significantly higher than those in vector group（7.91% and 5.56%,respectively）and CDDP group（24.51% and 22.22%,respec-tively）.Moreover,positive PCNA index in HNE-1 tumor in nanomedicine group（47.75%）was significantly lower than that in control group（90.83%）,vector group（89.62%）and CDDP group （68.43%）.Conclusion The constructed A-CM-β-CD-CDDP nanomedicine can inhibit the growth of FR-positive NPC tumor.