Tumor microenvironment remodeling-based penetration strategies to amplify nanodrug accessibility to tumor parenchyma

Remarkable advances in nano delivery systems have provided new hope for tumor prevention, diagnosis and treatment. However, only limited clinical therapeutic effects against solid tumors were achieved. One of the main reasons is the presence of abundant physiological and pathological barriers in vivo that impair tumoral penetration and distribution of the nanodrugs. These barriers are related to the components of tumor microenvironment (TME) including abnormal tumor vasculature, rich composition of the extracellular matrix (ECM), and abundant stroma cells. Herein, we review the advanced strategies of TME remodeling to overcome these biological obstacles against nanodrug delivery. This review aims to offer a perspective guideline for the implementation of promising approaches to facilitate intratumoral permeation of nanodrugs through alleviation of biological barriers. At the same time, we analyze the advantages and disadvantages of the corresponding methods and put forward possible directions for the future researches.