Abstract
A new class of apoferritin-based tunable nano-indicators, utilizing apoferritin (APO) as a template and the dye pair as a signal element, have been developed for intracellular pH sensing. Similar to cocktails making, the nano-indicator with a diameter of ∼10 nm can be flexibly and easily constructed just by mixing commercially available pH-sensitive and pH-insensitive dye pairs (without any derivatization) with APO in solution, based on the pH-dependent depolymerization/self-assembly properties of the bio-derived APO. By using different dye pairs (fluorescein/rhodamine B, fluorescein/RuBpy) for ratiometric design and controlling the dye feed ratio, the pH response performance of the APO-based nano-indicator including response linear range and sensitivity can be flexibly regulated. Compared with free dyes, it has lower cytotoxicity. Moreover, ratiometric signal of the nano-indicators can minimize the effect of system fluctuations, involving ambient temperature, probe local concentration and its solution environment. Furtherly, the nano-indicators have been successfully applied for intracellular pH measurement in the range of 5–7 and the detection of pH fluctuations in cells after different stimuli treatment.
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