Differential in situ sensing of extra- and intracellular glutathione by a novel redox-responsive silica matrix-Au nanoprobe

•A novel redox-responsive silica matrix was employed for AuNP nanoshell formation.•The distinct, sigmoidal dose–response pattern of nanoprobe toward thiols.•Rapid intracellular glutathione-sensing in cancer cells within 30 min.•Highly specific to carcinoma and non-responsive to normal cells.•Advantageous potential for future cancer theranostics.

We synthesized a biothiol-sensitive nanoprobe by assembling gold nanoparticles with a novel redox-responsive silica (ReSi) matrix using dithiobis (succinimidyl propionate) and (3-aminopropyl) trimethoxysilane. Thin layer disulfide-bonded networks of the ReSi could differentially respond to extra- and intracellular glutathione in cancer cells within 30 min; furthermore, targeted cellular uptake could be monitored in situ by fluorescence recovery. Sigmoidal dose–response pattern of the nanoprobes presented in this study were attributed to the buried disulfide-linked 3D nanostructure of the ReSi nanoshell, optimized at an appropriate thickness, enabling not only buffering of small redox disturbances in the extracellular milieu but also the satisfied sensitivity for rapid redox sensing. Such a ReSi-functionalized gold nanoparticle-based nanoconjugate possesses the potential to serve as an effective intracellular drug carrier for future cancer theranostics.

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