Multi-layered stimuli responsive DNA micelles for the stepwise controlled release of small molecules

Multi-layered stimuli responsive DNA micelles for the stepwise controlled release of small molecules
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DOI:
10.1039/d1tb02722k
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发表时间:
2022-02-28
影响因子:
7
通讯作者:
Rouge,Jessica L.
Rouge,Jessica L.
中科院分区:
工程技术2区
文献类型:
--
作者:
Santiana,Joshua J.;Sawant,Shraddha S.;Rouge,Jessica L.

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从纳米材料中可控释放多种不同的货物对于各种治疗和催化应用至关重要。在这项研究中,我们描述了一个DNA功能化的多层表面交联胶束(mlSCM)组成的单独降解层。DNA修饰的mlSCM具有将单独的小分子货物包封在纳米胶囊内的不同隔室中的能力,其通过化学交联剂分开。通过多步自组装过程中,我们表现出物理分离的内化货物证明了电子显微镜,沿着观察化学控制释放,和化学反应条件,如荧光光谱和高效液相色谱质谱分析。此外,我们通过体外共聚焦显微镜测定评估了这些DNA交联胶束将两种单独的货物共释放到相同细胞环境中的能力。我们展示了两种不同但相关的染料用于检测ATP和线粒体的个体化靶向。这些染料的共定位表明,与细胞呼吸相关的独特位置和信号可以使用单个mlSCM来识别。通过这些研究,我们最终表明,mlSCM具有可定制的设计,有可能应用于从传感到药物输送的众多应用。
Controllable release of multiple distinct cargoes from a nanomaterial is crucial to a variety of therapeutic and catalytic applications. In this study, we describe a DNA functionalized multi-layered surface crosslinked micelle (mlSCM) consisting of individually degradable layers. The DNA modified mlSCM has the ability to encapsulate separate small molecule cargo in distinct compartments within the nanocapsule, separated by chemical crosslinkers. Through a multistep self-assembly process, we show physical separation of internalized cargo as evidenced by electron microscopy, along with observation of chemical control over release, and chemical reaction conditions, as seen by fluorescence spectroscopy and a high-performance liquid chromatography mass spectrometry assay. Additionally, we evaluated the ability of these DNA crosslinked micelles to co-release two separate cargoes into the same cellular environment through an in vitro confocal microscopy assay. We show individualized targeting of two distinct but related dyes for the detection of ATP and mitochondria. The colocalization of these dyes indicates that unique locations and signals related to cellular respiration can be identified using a single mlSCM. Through these studies we ultimately show that the mlSCM has a tailorable design with the potential to be applied to numerous applications, ranging from sensing to drug delivery.