School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China.
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
ACS Appl Mater Interfaces. 2021 Sep 29;13(38):45291-45299. doi: 10.1021/acsami.1c13720. Epub 2021 Sep 20.
Dynamic imaging of cell surface pH is extremely challenging due to the slight changes in pH and the fast diffusion of secreted acid to the extracellular environment. In this work, we construct a novel metal-organic framework (MOF)-shell-confined i-motif-based pH probe (MOFC-i) strategy that enables sensitive and dynamic imaging of cell surface pH. The CY3- and CY5-labeled i-motif, which is hybridized via its short complementary chain with two-base mismatches, is optimized for sensing at physiological pH. After efficiently anchoring the optimized pH probes onto the cell membrane with the aid of cholesterol groups, a biocompatible microporous MOF shell is then formed around the cell by cross-linking ZIF-8 nanoparticles via tannic acid. The microporous MOF shell can confine secreted acid without inhibiting the normal physiological activities of cells; thus, the MOFC-i strategy can be used to monitor dynamic changes in the cell surface pH of living cells. Furthermore, this method can not only clearly distinguish the different metabolic behaviors of cancer cells and normal cells but also reveal drug effects on the cell surface pH or metabolism, providing promising prospects in pH-related diagnostics and drug screening.
由于 pH 值的微小变化和分泌酸向细胞外环境的快速扩散，对细胞表面 pH 值进行动态成像极具挑战性。在这项工作中，我们构建了一种新型的基于金属-有机框架（MOF）壳层限制的 i-motif 基 pH 探针（MOFC-i）策略，该策略能够对细胞表面 pH 值进行灵敏和动态成像。通过其短互补链与两个碱基错配杂交的 CY3 和 CY5 标记的 i-motif 在生理 pH 值下进行优化以用于感应。在胆固醇基团的帮助下，将优化的 pH 探针有效地锚定在细胞膜上之后，通过单宁酸交联 ZIF-8 纳米粒子在细胞周围形成了生物相容性的微孔 MOF 壳。微孔 MOF 壳可以限制分泌酸而不会抑制细胞的正常生理活动；因此，MOFC-i 策略可用于监测活细胞的细胞表面 pH 值的动态变化。此外，该方法不仅可以清楚地区分癌细胞和正常细胞的不同代谢行为，还可以揭示药物对细胞表面 pH 值或代谢的影响，为 pH 相关诊断和药物筛选提供了广阔的前景。
