We present a modular strategy to synthesize nanoparticle
sensors
equipped with dithiomaleimide-based, fluorescent molecular reporters
capable of discerning minute changes in interparticle chemical environments
based on fluorescence lifetime analysis. Three types of nanoparticles
were synthesized with the aid of tailor-made molecular reporters,
and it was found that protein nanoparticles exhibited greater sensitivity
to changes in the core environment than polymer nanogels and block
copolymer micelles. Encapsulation of the hydrophobic small-molecule
drug paclitaxel (PTX) in self-reporting protein nanoparticles induced
characteristic changes in fluorescence lifetime profiles, detected
via time-resolved fluorescence spectroscopy. Depending on the mode
of drug encapsulation, self-reporting protein nanoparticles revealed
pronounced differences in their fluorescence lifetime signatures,
which correlated with burst- vs diffusion-controlled release profiles
observed in previous reports. Self-reporting nanoparticles, such as
the ones developed here, will be critical for unraveling nanoparticle
stability and nanoparticle–drug interactions, informing the
future development of rationally engineered nanoparticle-based drug
carriers.