ABSTRACT: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.%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-cyclo-dextrin，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 10 mg·kg－1给药）1．5 h 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0．2 mL：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3 mg·kg－1的 CDDP 溶液，纳米药物组注射 FA-CM-β-CD-CDDP 溶液（含 CDDP 浓度3 mg·kg－1），给药后21 d 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 anti-gen，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。
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