Destruction of tumor vasculature by vascular disrupting agents in overcoming the limitation of EPR effect

Abstract

Nanomedicine greatly improves the efficiency in the delivery of antitumor drugs into the tumor, but insufficient tumoral penetration impairs the therapeutic efficacy of most nanomedicines. Vascular disrupting agent (VDA) nanomedicines are distributed around the tumor vessels due to the low tissue penetration in solid tumors, and the released drugs can selectively destroy immature tumor vessels and block the supply of oxygen and nutrients, leading to the internal necrosis of the tumors. VDAs can also improve the vascular permeability of the tumor, further increasing the extravasation of VDA nanomedicines in the tumor site, markedly reducing the dependence of nanomedicines on the enhanced permeability and retention effect (EPR effect). This review highlights the progress of VDA nanomedicines in recent years and their application in cancer therapy. First, the mechanisms of different VDAs are introduced. Subsequently, different strategies of delivering VDAs are described. Finally, multiple combination strategies with VDA nanomedicines in cancer therapy are described in detail.

Keywords: Tumor enrichment; Tumor internal necrosis; Vascular disrupting agents; Vascular permeability changes.