Nanomaterial (NM) delivery to solid tumors has been the focus of intense research for over a decade. Classically, scientists have tried to improve NM delivery by employing passive or active targeting strategies, making use of the so-called enhanced permeability and retention (EPR) effect. This phenomenon is made possible due to the leaky tumor vasculature through which NMs can leave the bloodstream, traverse through the gaps in the endothelial lining of the vessels, and enter the tumor. Recent studies have shown that despite many efforts to employ the EPR effect, this process remains very poor. Furthermore, the role of the EPR effect has been called into question, where it has been suggested that NMs enter the tumor via active mechanisms and not through the endothelial gaps. In this review, we provide a short overview of the EPR and mechanisms to enhance it, after which we focus on alternative delivery strategies that do not solely rely on EPR in itself but can offer interesting pharmacological, physical, and biological solutions for enhanced delivery. We discuss the strengths and shortcomings of these different strategies and suggest combinatorial approaches as the ideal path forward.

中文翻译：

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使用替代策略增强纳米粒子递送至实体瘤

十多年来，纳米材料 (NM) 向实体瘤的传递一直是深入研究的重点。传统上，科学家们试图通过采用被动或主动靶向策略，利用所谓的增强渗透性和保留 (EPR) 效应来改善 NM 递送。由于 NMs 可以通过渗漏的肿瘤血管系统离开血流，穿过血管内皮衬里的间隙并进入肿瘤，因此这种现象成为可能。最近的研究表明，尽管为利用 EPR 效应做出了许多努力，但这个过程仍然非常糟糕。此外，EPR 效应的作用也受到质疑，有人认为 NMs通过活性机制，而不是通过内皮间隙。在这篇综述中，我们简要概述了 EPR 和增强它的机制，之后我们专注于替代递送策略，这些策略不仅依赖于 EPR 本身，而且可以为增强递送提供有趣的药理学、物理和生物学解决方案。我们讨论了这些不同策略的优点和缺点，并建议将组合方法作为理想的前进道路。