文章：

克服生物物理屏障的创新治疗递送策略

Overcoming biophysical barriers with innovative therapeutic delivery approaches 

原文发布日期：2022-09-08 

英文摘要：

Cancer is often conceptualized as principally a cellular process, one initiated by genetic mutations in a progenitor cell that result in dysregulated cell proliferation. Accordingly, investigations into mechanisms of treatment resistance to cancer therapies often revolve around the biologic barriers to the therapies. However, there is a growing appreciation for the unique biomechanical properties for tumors and the role they play in treatment resistance for conventional, molecularly targeted, and immune-mediated cancer therapies. This understanding has inspired the development of pharmacologic and interventional approaches to overcome these barriers. Of particular promise are perfusion-enhanced drug delivery (PEDD) approaches that potentially allow for comprehensive tumor coverage with increased delivery pressure and prevention of reflux to drive therapeutics into the tumor parenchyma. In this review, we summarize the key features of the tumor microenvironment that drive tumor progression and impose barriers to anti-cancer therapies. We highlight the rationale and application of pharmacologic approaches and interventional drug delivery devices designed to overcome these impediments. We additionally contextualize these concepts by illustrating their application to the treatment of uveal melanoma liver metastases. 

摘要翻译： 

癌症通常被概念化为主要是一种细胞过程，始于祖细胞基因突变导致细胞增殖失调。因此，对癌症治疗耐药机制的研究往往围绕治疗的生物学障碍展开。然而，人们越来越认识到肿瘤独特的生物力学特性及其在传统治疗、分子靶向治疗和免疫介导的癌症治疗耐药性中的作用。这种认识推动了通过药理学和介入方法来克服这些障碍的研究。其中灌注增强药物递送（PEDD）技术尤其具有前景，它通过增加递送压力和防止返流将治疗药物驱动至肿瘤实质，可能实现肿瘤的全面覆盖。本综述总结了肿瘤微环境中驱动肿瘤进展并对抗癌治疗构成障碍的关键特征，重点探讨了旨在克服这些障碍的药理方法和介入式药物递送装置的原理与应用，并通过阐述这些技术在葡萄膜黑色素瘤肝转移治疗中的具体应用来进一步说明这些概念。

原文链接：

Overcoming biophysical barriers with innovative therapeutic delivery approaches