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纳米制剂具备高载药量、靶向性积聚以及表面修饰性质,被广泛应用于临床诊断和治疗,但是相关的毒性研究很少。为了研究白蛋白纳米制剂静脉注射后对正常组织的毒性,我们先通过高压均质法制备稳定、均一的紫杉醇白蛋白纳米粒,通过共价键将靶向肿瘤细胞HER2/neu受体的拟肽AHNP结合于纳米粒表面得到靶向修饰的纳米粒,并考察其理化性质。建立HER2受体过表达的荷瘤裸小鼠模型,静脉注射纳米制剂和紫杉醇传统注射液后取血进行血常规比较分析,发现紫杉醇白蛋白纳米粒和AHNP靶向修饰的紫杉醇白蛋白纳米粒均避免了传统注射液引起的粒细胞减少症和贫血作用。对动物肿瘤和重要组织进行病理切片、H&E染色分析,发现AHNP靶向修饰显著提高紫杉醇白蛋白纳米粒的抗肿瘤效果。紫杉醇白蛋白纳米粒和紫杉醇溶液均引起严重的肝损伤,AHNP靶向修饰能显著降低纳米粒对于肝脏的损伤,但可能增加个别动物的肺部损伤。
Nanoparticles with high drug loading, targeted accumulation and surface modification properties, are widely used in clinical diagnosis and treatment, but little toxicity related research. In order to study the toxicity of albumin nanoparticles to normal tissues after intravenous injection, we prepared stable and homogeneous paclitaxel albumin nanoparticles by high pressure homogenization, and then covalently linked the peptidomimetic targeting the tumor cell HER2 / neu receptor AHNP binds to the surface of nanoparticles to get targeted modification of nanoparticles, and examines its physical and chemical properties. To establish a tumor-bearing nude mouse model of HER2 receptor overexpression, intravenous injection of nano-formulations and conventional paclitaxel injection of blood for blood comparative analysis showed that paclitaxel albumin nanoparticles and AHNP targeted modified paclitaxel albumin nanoparticles were Avoid the traditional injection induced neutropenia and anemia. Pathological sections and H & E staining analysis of animal tumors and important tissues showed that AHNP targeted modification significantly enhanced the antitumor effect of paclitaxel albumin nanoparticles. Both paclitaxel nanoparticles and paclitaxel solution cause severe hepatic injury. Targeting modification of AHNP can significantly reduce the damage of the liver to the nanoparticles, but may increase the lung injury of individual animals.