Higher stability and reducibility of disulfide (DS) bonded micelles in serum, confirmed using FRET and the self-quenching properties of DOX. (a) Schematic illustrations of self-assembled (SA) and disulfide (DS) bonded micelles with FRET dyes (DiO and DiI) or doxorubicin (DOX). (b) Time-resolved spectra of SA and DS FRET micelles in 80% (v/v) FBS without or with 10 mM GSH at 37°C. FRET ratio, IDiI/(IDiI+IDiO), as a function of incubation time. IDiI and IDiO represent the fluorescence intensities of DiI at 570 nm and DiO at 508 nm in the spectrum measurements. (c) Time-lapse spectra of DOX/SA and DOX/DS micelles in 80% (v/v) FBS without or with 10 mM GSH at 37°C. Recovery of DOX fluorescence intensity, ((F-FW)/FD)×100, as a function of incubation time. FW and FD correspond to the integrated fluorescence for the micelles in water and DMSO with 100 mM DTT.