平阳霉素-活性炭纳米微粒行口腔癌淋巴化疗的靶向性评价

Lymphatic targeting study of pingyangmycin-activated carbon nanoparticles treating oral cancer lymph node metastasis

目的观察平阳霉素-活性炭纳米微粒(PYM-CH-NP)经鼠癌周黏膜下给药后,活性药物在体内各组织器官中的分布情况,探讨PYM-CH-NP对淋巴结转移灶的靶向性。方法采用改良氯胺T法将125I标记平阳霉素(PYM),应用淋巴结高转移癌株U14建立昆明小鼠颈淋巴结转移模型。将360只颈淋巴结转移模型小鼠随机分为PYM-CH-NP组、PYM组和阴性对照组,分别于癌周黏膜下注射PYM-CH-NP、PYM水溶液和空白活性炭纳米微粒,给药后0.5、1、4、8、12、24、48、72、96、120、144、168 h处死动物,取血、心、肝、脾、肺、肾和颈淋巴结,检测各时间点各组织器官内平阳霉素的放射活性,计算各样本单位重量的药物放射活性(比放射活性),并计算药物的选择性指数(SI)和靶向指数(TI)。结果 PYM-CH-NP组各时间点颈淋巴结内药物浓度显著高于PYM组(P<0.001),4 h后血、心、肝、脾、肺、肾等器官中药物浓度均低于PYM组(P<0.001)。PYM组各时间点的SI均小于1,而PYM-CH-NP组SI和TI最低值为1.793和1.562,最高为72 h时的68.126和14.623。结论 PYM-CH-NP可显著增加淋巴结转移灶内的药物浓度,同时非靶器官药物分布减少,降低了药物的全身毒副反应。

Objective To investigate the drug distribution in tissues of cervical lymph node metastasis mice model after submucosa adjacent cancer injection of pingyangmycin-activated carbon nanoparticles（PYM-CH-NP） and evaluate the lymph targeting effect of PYM-CH-NP.Methods Pingyangmycin（PYM） was radiolabeled with 125I by modified the chloramine T method.Cervical lymph node metastasis mice model was established by buccal submucosa inoculation of a high lymph metastasis cell line U14 cancer cell.360 mice models burdened with cervical lymph metastasis were ran-domly divided into 3 groups.PYM group was treated with PYM water solution,PYM-CH-NP group was treated with PYM-CH-NP.Negative control group was injected with activated carbon nanoparticles.PYM-CH-NP and pingyangmycin water solution were injected in pericancer submucosa of the mice respectively.The radioactivity of drug in blood,heart,liver,spleen,lung,kidney and cervical lymph node were measured after 0.5,1,4,8,12,24,48,72,96,120,144,168 h administration.The radioactivity of each samples per unit weight were calculated.The selectivity index（SI） and targeting index（TI） of drug were calculated.Results The radioactivity of drug in cervical lymph node of PYM-CH-NP group was much higher than PYM group in each time point（P0.001）,whereas the blood,heart,liver,spleen, lung and kidney uptake of pingyangmycin was greatly decreased in PYM-CH-NP group after 4 h administration（P 0.001）.The SI value of PYM group at each time point was less than 1.While the minimum SI and TI value of PYM-CH-NP was 1.793 and 1.562,the maxlmum value reached to 68.126 and 14.623 after 72 h administration.Conclusion PYM-CH-NP can increase drug dosage in metastasized cervical lymph nodes,and decrease drug dosage of other organs.So better therapeutic outcome and little adverse reaction may be achieved for lymph node metastasis.