阿霉素纳米微粒靶向治疗舌鳞癌的实验研究

Experimental study of target-specific adriamycin nanoparticles in treating tongue squamous cell carcinoma

目的:研究阿霉素纳米微粒经兔舌动脉给药后,舌癌病灶及易损器官的药物分布,确定阿霉素纳米微粒治疗舌癌的靶向性。方法:将30只荷舌癌的纯种新西兰白兔随机分为阿霉素组和阿霉素纳米微粒组,每组15只。分别将阿霉素和聚氰基丙烯酸正丁脂阿霉素纳米微粒(平均粒径93.1nm±11.7nm),通过超选择舌动脉导管给药(药物剂量2mg/kg、药物浓度1mg/ml)。每组给药后1、5、15h分别处死5只兔,取舌、舌癌、心、肝、脾、肾组织各1.0g,血浆1ml,用高效液相色谱法检测组织和血浆内的药物浓度,对所得数据进行t检验。结果:1、5、15h阿霉素纳米微粒组在舌肿瘤和舌组织内的药物含量显著高于游离阿霉素组(P<0.01);而非靶器官心、肝等药物浓度显著降低,差别有显著性差异(P<0.01)。结论:阿霉素纳米微粒经舌动脉给药,可以显著增加抗癌药物的靶向性,增加药物疗效,同时由于非靶器官药物浓度减少,降低了药物的毒副作用。

PURPOSE： This study was designed to explore the method for increasing the target-specific action of anticancer agent in treating tongue squamous cell carcinoma. METHODS： 30 purebred New Zealand rabbits burdened with tongue squamous cell carcinoma were randomly divided into 2 groups.Group A was treated with adriamycin and group B treated with adriamycin nanoparticles, with 15 animals in each group. The adriamycin and poly （buty1-2-cyanoacrylate） adriamycin nanoparticles （mean diameter 93.1 nm±11.7nm） with 1mg/ml in concentration were administered respectively to subjects through super-selective lingual arterial tuber. The dose was 2mg/kg for each group. 1,5 and 15 hours after administration, 5 subjects were sacrificed and the tongue, carcinoma in tongue tissue, heart, liver, spleen, kidney and plasma were examined through high performance liquid chromatography（HPLC） to identify the drug concentration. The data then underwent Student＇s t test. RESULTS ：The drug concentration in the tongue and carcinoma in group B were significantly higher than those in group A （P〈0.01）. The drug concentration in heart, liver, spleen, kidney and plasma of group B were significantly lower than those of group A （P〈0.01）. CONCLUSION：The super-selective lingual arterial administration of adriamycin nanoparticles can reinforce the target-specific action of anticancer agent, increase the drug concentration within the lesion and decrease it in non-specific organs. Supported by Shanghai Leading Academic Discipline Project （Grant No.Y0203）.