Rational design of a cancer-specific and lysosome-targeted fluorescence nanoprobe for glutathione imaging in living cells

Developing versatile probe for targeting the lysosome of specific cancer cells and subsequently detecting glutathione (GSH) levels is critical in disclosing the roles of GSH in lysosomal oxidative stress of cancer cells. Herein, we demonstrate an efficient strategy for dual-targeting (both cancer cells and lysosome targeting) fluorescence nanoprobe (DTFN) that enables imaging of GSH in lysosome of specific cancer cells. The nanoprobe (DTFN) is obtained by combining the folic acid (FA)-modified photostable aggregation-induced emission dots with GSH-responsive manganese dioxide (MnO2) nanosheet via electrostatic interaction. The DTFN has outstanding characteristics of good water dispersity, delightful photostability, shorter responsive time (~5 min) and wide pH response range. Intracellular experiments showed that the as-prepared DTFN could be preferentially internalized into folate receptor (FR)-positive cancer cells through FR-mediated endocytosis. Subsequently, with the aid of the positive charge amino moiety of the nanoprobe, the DTFN can selectively accumulate in lysosomes and successfully achieve for real-time imaging of lysosomal GSH levels in FR-positive cancer cells. This study highlights a strategy to design versatile dual-targeting fluorescence probe for enhanced cancer imaging.