抗癌纳米微粒行口腔癌淋巴化疗的疗效观察和药物体内组织分布的实验研究

Therapeutic effect and drug tissue distribution of anticancer nanoparticles for lymphochemotherapy in oral cancer mice model

目的 探讨平均粒径为 85nm的抗癌纳米微粒行口腔癌淋巴化疗的治疗疗效和药物在体内的组织分布情况。方法 用高颈淋巴结转移癌株U14 建立昆明小鼠颊癌颈淋巴结转移模型 ,以平均粒径为 85nm的葫芦素BE聚乳酸抗癌纳米微粒 (CuBE -PLA -NP)为实验组 ,以抗癌药物葫芦素BE (CuBE)为阳性对照 ,空白纳米微粒 (PLA -NP)为阴性对照 ,分别行癌周黏膜下注射 ,注射后在 15个不同时间点处死动物 ,用高效液相色谱仪检测血、心、肝、脾、肺、肾和颈淋巴结内在不同时间点的药物浓度 ,以考察药物在体内的组织分布情况 ,并观察各组对颈淋巴结转移灶的治疗效果。结果 实验组中颈淋巴结转移灶内药物相对百分比远远高于对照组 (P <0 .0 5 ) ,实验组中颈淋巴结转移灶的平均重量低于两对照组 (P <0 .0 5 ) ,在用药 12h后 ,实验组中颈淋巴结转移癌细胞可见有明显坏死 ,随着时间延长 ,颈转移灶内坏死区域增大 ,而两对照组中颈淋巴结转移癌细胞在各个时间点均未出现坏死。结论 平均粒径为 85nm的CuBE -PLA

objective To investigate therapeutic effect and drug tissue distribution of the average diameter 85 nm Anticancer Nanoparticles for lymphochemotherapy in oral Cancer in vivo.Methods Established oral Cancer Cervical lymph node metastasis model in mice. Anticancer Nanoparticles(CucurbitacinBE Polylactic Acid Nanoparticles,CuBE-PLA-NP) is injected in pericancer Submucosal of model mice,compared with injection of CuBE(positive control group) and PLA-NP (negative control group)respectively,the drug concentration of blood?heart?liver?slpeen?lung?kidney and cervical lymph node are measured by high performance liquid chromatography at the fifteen time points,therapeutic effect and drug tissue distribution are evaluated.Results Drug relative percentage in cervical lymph node of CuBE-PLA-NPgroup are far higher than that either CuBE group or PLA-NP group ( p < 0.05 ),the average weight of cervical lymph node metastaic foci in CuBE-PLA-NP group are lower than that in two control groups ( p < 0.05 ). metastaic cancer cell in cervical lymph node of CuBE-PLA-NP group showed necrosis at 12 h after injecting CuBE-PLA-NP,with time prolonging,necrotic area become gradually large,however,necrosis of cancer cell was not found in positive control group and negative control group at all time points.Conclusion The average diameter 85nm anticancer nanoparticles can specifically deliver anticancer drug to the cervical lymph node metastaic foci by pericancer Submucosal injection,enhancing drug therapeutic effect.