Quantitative Measurement of Drug Release Dynamics within Targeted Organelles Using Förster Resonance Energy Transfer

Abstract Measuring the release dynamics of drug molecules after their delivery to the target organelle is critical to improve therapeutic efficacy and reduce side effects. However, it remains challenging to quantitatively monitor subcellular drug release in real time. To address the knowledge gap, a novel gemini fluorescent surfactant capable of forming mitochondria‐targeted and redox‐responsive nanocarriers is designed. A quantitative Förster resonance energy transfer (FRET) platform is fabricated using this mitochondria‐anchored fluorescent nanocarrier as a FRET donor and fluorescent drugs as a FRET acceptor. The FRET platform enables real‐time measurement of drug release from organelle‐targeted nanocarriers. Moreover, the obtained drug release dynamics can evaluate the duration of drug release at the subcellular level, which established a new quantitative method for organelle‐targeted drug release. This quantitative FRET platform can compensate for the absent assessment of the targeted release performances of nanocarriers, offering in‐depth understanding of the drug release behaviors at the subcellular targets.