Department of Biomedical Engineering and Mechanics, Virginia Tech, 325 Stanger St, Blacksburg, VA, 24061, USA.
Department of Biomedical Sciences and Pathobiology, VA-MD College of Veterinary Medicine, Virginia Tech, 205 Duck Pond Drive, Blacksburg, VA, 24061, USA.
Ann Biomed Eng. 2024 Jan;52(1):48-56. doi: 10.1007/s10439-023-03403-x. Epub 2023 Nov 21.
This study introduces a new method of targeting acidosis (low pH) within the tumor microenvironment (TME) through the use of cathodic electrochemical reactions (CER). Low pH is oncogenic by supporting immunosuppression. Electrochemical reactions create local pH effects when a current passes through an electrolytic substrate such as biological tissue. Electrolysis has been used with electroporation (destabilization of the lipid bilayer via an applied electric potential) to increase cell death areas. However, the regulated increase of pH through only the cathode electrode has been ignored as a possible method to alleviate TME acidosis, which could provide substantial immunotherapeutic benefits. Here, we show through ex vivo modeling that CERs can intentionally elevate pH to an anti-tumor level and that increased alkalinity promotes activation of naïve macrophages. This study shows the potential of CERs to improve acidity within the TME and that it has the potential to be paired with existing electric field-based cancer therapies or as a stand-alone therapy.
这项研究介绍了一种通过使用阴极电化学反应（CER）靶向肿瘤微环境（TME）中酸中毒（低 pH 值）的新方法。低 pH 值通过支持免疫抑制而致癌。当电流通过生物组织等电解基质时，电化学反应会产生局部 pH 效应。电解已与电穿孔（通过施加电场使脂质双层不稳定）一起使用，以增加细胞死亡区域。然而，通过阴极电极仅调节 pH 值的增加已被忽视为缓解 TME 酸中毒的一种可能方法，这可能会提供实质性的免疫治疗益处。在这里，我们通过离体模型表明 CER 可以有意将 pH 值升高到抗肿瘤水平，并且增加的碱度促进了幼稚巨噬细胞的激活。这项研究表明了 CER 改善 TME 内酸度的潜力，并且有可能与现有的基于电场的癌症疗法结合使用，或作为单独的疗法。
