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The integration of triggered drug delivery with real time quantification using FRET; creating a super ‘smart’ drug delivery system
Journal of Controlled Release ( IF 10.8 ) Pub Date : 2017-08-18 , DOI: 10.1016/j.jconrel.2017.08.013
Noorjahan Aibani , Paola Fontoura da Costa , Jodie Masterson , Nino Marino , Françisco M. Raymo , John Callan , Bridgeen Callan

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.



中文翻译:

使用FRET将触发的药物输送与实时定量相结合; 创建一个超级“智能”药物输送系统

控制药物在特定生理靶标上释放的能力使得可以提高治疗效果,同时降低靶标外的毒副作用。药物控制释放的学科已经发展到包括医学的大多数领域,并在文献中列举了将药物靶向人体大部分器官的例子。另外,还研究了用于冥想药物释放过程的各种外部刺激。尽管如此,并没有实时研究药物释放的实时监控。在本手稿中,我们介绍了一种新型的胶束药物递送系统,该系统不仅能够在光线刺激下释放其货物,而且还可以对剩余货物的数量进行实时分析。螺吡喃-花青光致变色二倍体的物理化学变化介导了药物从递送系统的释放,而光致变色剂和共包封的BODIPY荧光团之间的福斯特共振能量转移(FRET)关系实现了药物定量分析。与在黑暗中维持的类似对照相比,当暴露于光照射下时,从递送系统释放的药物百分比显着更高(24%)。此外,与在黑暗中维持的对照细胞相比,荧光读出能力还使得能够在活细胞中追踪药物释放过程,对于那些与递送系统一起孵育并暴露于光照射的细胞,观察到的荧光发射显着降低。结合起来

更新日期:2017-08-18
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