Abstract

Introduction

The enhanced permeability and retention (EPR) effect serves as the foundation of anticancer nanomedicine design. EPR effect-based drug delivery is an effective strategy for most solid tumors. However, the degree of efficacy depends on the pathophysiological conditions of tumors, drug formulations, and other factors.

Areas covered

Vascular mediators including nitric oxide (NO), bradykinin (BK), and prostaglandins (PGs) are vital for facilitating and maintaining EPR effect dynamics. Progression to large, advanced cancers may induce activated blood coagulation cascades, which lead to thrombus formation in tumor vasculature. Rapidly growing tumors cause obstructed or suppressed blood flow in tumor vasculature related to embolism or occluded blood vessels. The resulting limited tumor blood flow leads to less drug delivered to tumors, i.e. no or poor EPR effect. High stromal content also suppresses vascular permeability and drug diffusion. Restoring obstructed tumor blood flow and improving tumor vascular permeability via vascular mediators will improve drug delivery and the EPR effect. Physicochemical features of nanomedicines also influence therapeutic outcomes and are vital for the EPR effect.

Expert opinion

The tumor microenvironment, especially tumor blood flow, is critical for a potent EPR effect. A rational strategy for circumventing EPR effect barriers must include restoring tumor blood flow.

中文翻译：

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影响EPR效应的动力学和异质性的因素：病理生理和病理解剖特征，药物制剂和理化因素

摘要

介绍

增强的渗透性和保留（EPR）效果是抗癌纳米药物设计的基础。基于EPR效应的药物递送是大多数实体瘤的有效策略。但是，功效的程度取决于肿瘤的病理生理状况，药物制剂和其他因素。

覆盖区域

包括一氧化氮（NO），缓激肽（BK）和前列腺素（PG）在内的血管介导物对于促进和维持EPR效应动力学至关重要。进展为大型晚期癌症可能会诱导激活的凝血级联反应，从而导致肿瘤脉管系统中形成血栓。快速生长的肿瘤导致与栓塞或血管闭塞有关的肿瘤脉管系统中的血流受阻或抑制。导致的有限的肿瘤血流导致较少的药物递送至肿瘤，即没有或不良的EPR作用。高基质含量也抑制血管渗透性和药物扩散。通过血管介导物恢复受阻的肿瘤血流并改善肿瘤的血管通透性，将改善药物的递送和EPR效果。

专家意见

肿瘤微环境，尤其是肿瘤血流，对于有效的EPR效应至关重要。规避EPR效应障碍的合理策略必须包括恢复肿瘤血流。