细胞外pH值改变与各种病理状况之间的相关性,包括癌症,炎症和代谢紊乱,是众所周知的。整体pH测量不能报告细胞表面的细胞外pH值。然而,有有限数量的合适的工具来测量细胞的细胞外pH具有高空间分辨率,它们都不常用于世界各地的实验室。在这项研究中,开发了一种用于测量细胞外pH的通用比率纳米传感器。纳米传感器由装载有pH惰性参考染料尼罗红的生物相容性聚苯乙烯纳米颗粒组成,并用pH响应性荧光素染料进行表面官能化。配有靶向部分,纳米传感器可以粘附在细胞膜上,允许直接测量细胞表面的细胞外pH。纳米传感器表现出在5.5-9.0范围内的灵敏比例pH响应,计算的pKa为7.47。该范围最佳地涵盖了大多数健康细胞和pHe异常的细胞的细胞外pH(pHe)。如癌细胞。结合纳米传感器靶向细胞膜的能力,它的高鲁棒性,可逆性及其生物相容性,phe纳米传感器被证明非常适合细胞外pH的原位测量,即使在延长的时间内。这种pH纳米传感器有可能通过提高我们对细胞微环境的理解来推进生物医学研究,其中细胞外pH起着重要作用。
The correlation between altered extracellular pH and various pathological conditions, including cancer, inflammation and metabolic disorders, is well known. Bulk pH measurements cannot report the extracellular pH value at the cell surface. However, there is a limited number of suitable tools for measuring the extracellular pH of cells with high spatial resolution, and none of them are commonly used in laboratories around the world. In this study, a versatile ratiometric
nanosensor for the measurement of extracellular pH was developed. The
nanosensor consists of biocompatible polystyrene nanoparticles loaded with the pH-inert reference dye Nile red and is surface functionalized with a pH-responsive fluorescein dye. Equipped with a targeting moiety, the
nanosensor can adhere to cell membranes, allowing direct measurement of extracellular pH at the cell surface. The
nanosensor exhibits a sensitive ratiometric pH response within the range of 5.5-9.0, with a calculated pKa of 7.47. This range optimally covers the extracellular pH (pHe) of most healthy cells and cells in which the pHe is abnormal, such as cancer cells. In combination with the nanosensors ability to target cell membranes, its high robustness, reversibility and its biocompatibility, the pHe nanosensor proves to be well suited for in-situ measurement of extracellular pH, even over extended time periods. This pH
nanosensor has the potential to advance biomedical research by improving our understanding of cellular microenvironments, where extracellular pH plays an important role.