三维肿瘤细胞模型在纳米载体性能评价中的应用

Application of 3D Tumor Spheroids in Evaluation of Nanocarriers

纳米载体能够通过高渗透长滞留效应或主动靶向识别作用在肿瘤组织中聚集,介导药物在动物体内进行选择性分布,从而提高抗肿瘤的治疗效果。纳米载体的尺寸、形状、表面电荷、表面配体修饰等自身特性对其在肿瘤组织中的靶向渗透具有重要的调控作用。相较于二维单层培养的肿瘤细胞,三维肿瘤细胞模型能够更好地模拟体内肿瘤组织的物理结构、化学组成和生物学特点,近年来被较多地应用于纳米载体瘤内渗透及治疗效果的评价研究。综述三维肿瘤细胞模型的特点和制备方法,总结其应用于研究纳米载体渗透肿瘤组织的影响因素、载药纳米颗粒的治疗效果以及纳米载体毒性评价的进展,探讨其在纳米载体性能评价应用中的发展趋势。

Nanocarriers may selectively accumulate in tumor tissues through enhanced permeability and retention effect(EPR)or actively targeting functions,and thereby improve the therapeutic efficacy.A range of physicochemical parameters including the size,shape,surface charge,and ligands attachment have been found influencing penetration of nanocarriers in the tumor tissue.Compared with two-dimensional(2D)monolayer cell cultures,three-dimensional(3D)tumor spheroids can better mimic the characteristics of the natural tumor tissues,and therefore have been widely used in the evaluation of tumor penetration and therapeutic efficacy of nanocarriers in recent years.In this review,we will introduce the properties and the preparation methods of 3D tumor spheroids,summarize recent studies investigating the interaction between nanoparticles and 3D tumor spheroids,and discuss the factors that affect the penetration behaviors,therapeutic effects and the intrinsic toxicity of nanocarriers.