The integration of triggered drug delivery with real time quantification using FRET; creating a super ‘smart’ drug delivery system

Abstract

The ability to control drug release at a specific physiological target enables the possibility of an enhanced therapeutic effect with reduced off-target toxic side effects. The discipline of controlled drug release has grown to include most areas of medicine with examples in the literature of targeted drug delivery to the majority of organs within the human body. In addition, a variety of external stimuli used to meditate the drug release process have also been investigated. Nonetheless, the concurrent real time monitoring of drug release has not been widely studied. In this manuscript, we present a novel micellar drug delivery system that is not only capable of releasing its cargo when stimulated by light but also provides a real time analysis of the amount of cargo remaining. Controlled drug release from the delivery system was mediated by physicochemical changes of a spiropyran-merocyanine photochromic dyad, while drug quantification was enabled using a Förster Resonance Energy Transfer (FRET) relationship between the photochrome and a co-encapsulated BODIPY fluorophore. The percentage of drug released from the delivery system was significantly greater (24%) when exposed to light irradiation compared to an analogous control maintained in the dark (5%). Furthermore, the fluorescence read-out capability also enabled the drug-release process to be followed in living cells with a significantly reduced fluorescence emission observed for those cells incubated with the delivery system and exposed to light irradiation compared to control cells maintained in the dark. Combined, these results highlight the utility of this approach to theranostic drug delivery with the potential of light-triggered released together with a fluorescence read-out to enable quantification of the drug release process.