通过增加EPR效应提高抗肿瘤药物递送效率的研究进展

Strategies to Improve Antitumor Drug Delivery by Increasing EPR Effect

在过去的几十年里,高渗透强滞留效应(enhanced permeability and retention effect,EPR)成为抗肿瘤药物靶向递送的主要理论基础。由于EPR效应的问世,纳米技术在抗肿瘤研究领域引起了更多的关注。然而,由于复杂的肿瘤微环境、肿瘤异质性、小鼠肿瘤模型与临床肿瘤模型的差异,基于EPR效应的新药研究在临床试验中表现远低于预期。因此,研究者们从不同角度进行了很多探索,笔者从改善肿瘤微环境、纳米粒子的设计和修饰、物理辅助等方面综述了近年来提高EPR效应的策略,以及不依赖EPR效应的抗肿瘤药物递送技术,为抗肿瘤纳米药物的设计和临床转化提供新视角。

In the past few decades,the enhanced permeability and retention effect(EPR)has been considered as the main theoretical base underlying the tumor targeted delivery of many drugs.Due to the advent of EPR effect,nanotechnology and nanomedicine have reached an unprecedented level in anti-tumor research.However,the complex tumor micro-environment and tumor heterogeneity together with the significant difference between mice-tumor models and human tumors led to the far short of expectation of EPR effect-based nanomedicine in the clinical trials for tumor treatment.In order to overcome this challenge,researchers have made a lot of efforts and explorations in different fields.In this review,the strategies recently developed to improve the EPR effect including those through the tumor micro-environment improvement,the rational design and modification of nanoparticles,and those assisted by physiotherapy,are summarized.In addition,the new strategies recently discovered that are independent on the EPR effect but successful in helping nanomedicine to penetrate into tumor are introduced as well to provide a new perspective for the design of nanomedicines and their clinical translation.