State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing, 100029, China.
Green Catalysis Center, College of Chemistry, Zhengzhou University, Zhengzhou, 450001, China.
Small. 2023 Jul;19(28):e2206866. doi: 10.1002/smll.202206866. Epub 2023 Apr 7.
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.
测量药物分子在递送到靶细胞器后的释放动力学对于提高治疗效果和降低副作用至关重要。然而，实时定量监测亚细胞药物释放仍然具有挑战性。为了解决这一知识空白，设计了一种新型的双子荧光表面活性剂，能够形成靶向线粒体和氧化还原响应的纳米载体。使用这种锚定在线粒体上的荧光纳米载体作为 FRET 供体和荧光药物作为 FRET 受体，构建了一个定量的Förster 共振能量转移（FRET）平台。该 FRET 平台能够实时测量细胞器靶向纳米载体中药物的释放。此外，所获得的药物释放动力学可以评估亚细胞水平药物释放的持续时间，为细胞器靶向药物释放建立了一种新的定量方法。这种定量 FRET 平台可以弥补纳米载体靶向释放性能评估的缺失，深入了解亚细胞靶标处的药物释放行为。
