Pérez-Herrero Edgar, Fernández-Medarde Alberto
Departamento de Ingeniería Química y Tecnología Farmacéutica, Universidad de La Laguna, La Laguna 38206, Tenerife, Spain.
Instituto Universitario de Bio-Orgánica Antonio González, Universidad de La Laguna, La Laguna 38206, Tenerife, Spain.
Acta Pharm Sin B. 2021 Aug;11(8):2243-2264. doi: 10.1016/j.apsb.2021.01.012. Epub 2021 Jan 24.
Solid tumors are complex entities, comprising a wide variety of malignancies with very different molecular alterations. Despite this, they share a set of characteristics known as "hallmarks of cancer" that can be used as common therapeutic targets. Thus, every tumor needs to change its metabolism in order to obtain the energy levels required for its high proliferative rates, and these adaptations lead to alterations in extra- and intracellular pH. These changes in pH are common to all solid tumors, and can be used either as therapeutic targets, blocking the cell proton transporters and reversing the pH changes, or as means to specifically deliver anticancer drugs. In this review we will describe how proton transport inhibitors in association with nanocarriers have been designed to block the pH changes that are needed for cancer cells to survive after their metabolic adaptations. We will also describe studies aiming to decrease intracellular pH in cancer using nanoparticles as molecular cages for protons which will be released upon UV or IR light exposure. Finally, we will comment on several studies that have used the extracellular pH in cancer for an enhanced cell internalization and tumor penetration of nanocarriers and a controlled drug delivery, describing how nanocarriers are being used to increase drug stability and specificity.
实体瘤是复杂的实体，由具有非常不同分子改变的多种恶性肿瘤组成。尽管如此，它们具有一组被称为“癌症标志”的特征，可作为共同的治疗靶点。因此，每个肿瘤都需要改变其代谢，以获得其高增殖率所需的能量水平，而这些适应性变化会导致细胞外和细胞内pH值的改变。pH值的这些变化在所有实体瘤中都很常见，既可以用作治疗靶点，通过阻断细胞质子转运体并逆转pH值变化来实现，也可以作为特异性递送抗癌药物的手段。在这篇综述中，我们将描述质子转运抑制剂与纳米载体联合使用是如何设计的，以阻断癌细胞在代谢适应后存活所需的pH值变化。我们还将描述旨在利用纳米颗粒作为质子分子笼来降低癌细胞内pH值的研究，这些质子在紫外线或红外线照射下会释放出来。最后，我们将对几项利用癌症细胞外pH值来增强纳米载体的细胞内化和肿瘤渗透以及实现可控药物递送的研究进行评论，描述纳米载体是如何被用于提高药物稳定性和特异性的。
