Cysteine-loaded pH-responsive liposome/gold nanoparticles as a time-temperature indicator with instantaneous color change

Abstract A novel time-temperature indicator (TTI) with instantaneous color change was developed by applying cysteine-loaded pH-responsive liposome/gold nanoparticles (Cys-pRL/AuNP) as a pH indicator to the glucose oxidase/glucose (GOx/Glu) TTI. It was hypothesized that the pH change caused by gluconic acid production causes cysteine release from the Cys-pRL, resulting in the AuNP aggregation (red→blue) at the pRL critical pH. The Cys-pRL with a lipid bilayer (phosphatidylcholine/dioleoylphosphatidylethanolamine/cholesterol/oleic acid in molar ratio of 24/24/40/12) was prepared by the freeze-drying method. The spherical morphology of the Cys-pRL was confirmed from TEM micrographs. FTIR analysis revealed that the cysteine was captured in the Cys-pRL. The critical pH of the pRL was found to be 4.0–4.7 by using [Cys-pRL/AuNP]/HCl. [Cys-pRL/AuNP]/[GOx/Glu] TTI showed the instantaneous color change in a narrow transition zone (pH 4.0–4.6), whereas a conventional TTI with regular pH indicator bromocresol green/[GOx/Glu] showed the gradual color change in a wide transition zone (pH 3.9–6.1).