Extracellular pH impacts many molecular, cellular and physiological processes, and hence is tightly regulated. Yet, in tumours, dysregulated cancer cell metabolism and poor vascular perfusion cause the tumour microenvironment to become acidic. Here by leveraging fluorescent pH nanoprobes with a transistor-like activation profile at a pH of 5.3, we show that, in cancer cells, hydronium ions are excreted into a small extracellular region. Such severely polarized acidity (pH <5.3) is primarily caused by the directional co-export of protons and lactate, as we show for a diverse panel of cancer cell types via the genetic knockout or inhibition of monocarboxylate transporters, and also via nanoprobe activation in multiple tumour models in mice. We also observed that such spot acidification in ex vivo stained snap-frozen human squamous cell carcinoma tissue correlated with the expression of monocarboxylate transporters and with the exclusion of cytotoxic T cells. Severely spatially polarized tumour acidity could be leveraged for cancer diagnosis and therapy.

细胞外 pH 值影响许多分子、细胞和生理过程，因此受到严格调节。然而，在肿瘤中，癌细胞代谢失调和血管灌注不良导致肿瘤微环境变成酸性。在这里，通过利用在 pH 值为 5.3 时具有类似晶体管激活曲线的荧光 pH 纳米探针，我们表明，在癌细胞中，水合氢离子被分泌到一个小的细胞外区域。这种严重极化的酸度（pH <5.3）主要是由质子和乳酸的定向共输出引起的，正如我们通过基因敲除或单羧酸转运蛋白抑制以及通过纳米探针激活在多种癌细胞类型中所显示的那样。小鼠的多种肿瘤模型。我们还观察到，离体染色的速冻人鳞状细胞癌组织中的这种点酸化与单羧酸转运蛋白的表达以及细胞毒性T细胞的排除相关。严重空间极化的肿瘤酸度可用于癌症诊断和治疗。