Silica-Coated Quantum Dots for Optical Evaluation of Perfluorocarbon Droplet Interactions with Cells
Silica-Coated Quantum Dots for Optical Evaluation of Perfluorocarbon Droplet Interactions with Cells
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DOI：
10.1021/la202679p
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发表时间：
2011-12-20
期刊：
影响因子：
3.9
通讯作者：
Matsuura, Naomi
中科院分区：
文献类型：
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作者：
Gorelikov, Ivan;Martin, Amanda L.;Matsuura, Naomi
最近人们对开发用于医学成像的新的、靶向的、基于全氟化碳（PFC）液滴的造影剂（例如，磁共振成像、X射线/计算机断层扫描和超声成像）。然而，由于大量潜在的PFC和液滴稳定策略可用，因此提前确定PFC液滴配方具有挑战性，该配方将导致临床成功所需的最佳体内行为和成像性能。我们建议将荧光量子点（QD）整合到新的PFC液滴试剂中，可以帮助快速筛选新的PFC候选试剂，以便在其开发早期获得生物相容性。QD标记可以允许使用体外光学方法以高灵敏度和分辨率评估PFC液滴与单细胞的相互作用，补充使用体内医学成像系统的PFC液滴成像提供的更深的深度穿透但更低的分辨率。在这项工作中，我们引入了一种简单而稳健的方法，通过与1H，1H，2 H，2 H-全氟癸基三乙氧基硅烷的水解-缩合反应对二氧化硅表面进行氟化，将二氧化硅涂层纳米颗粒混溶为疏水性和疏脂性PFCs。使用CdSe/ZnS核/壳量子点，我们表明，纳米级，量子点标记的PFC液滴可以很容易地形成，与未标记的PFC液滴的大小和表面电荷相似。QD标记可用于通过荧光显微镜和流式细胞术测定PFC液滴在体外细胞中的摄取，并可用于通过组织学组织切片的荧光显微镜验证PFC液滴在小动物体内的命运。这分别在巨噬细胞和癌细胞以及兔子中得到证实。这项工作揭示了使用QD标签对不同PFC液滴制剂进行快速、临床前、光学评估的潜力，以便将来用于患者。
There has been recent interest in developing new, targeted, perfluorocarbon (PFC) droplet-based contrast agents for medical imaging (e.g., magnetic resonance imaging, X-ray/computed tomography, and ultrasound imaging). However, due to the large number of potential PFCs and droplet stabilization strategies available, it is challenging to determine in advance the PFC droplet formulation that will result in the optimal in vivo behavior and imaging performance required for clinical success. We propose that the integration of fluorescent quantum dots (QDs) into new PFC droplet agents can help to rapidly screen new PFC-based candidate agents for biological compatibility early in their development. QD labels can allow the interaction of PFC droplets with single cells to be assessed at high sensitivity and resolution using optical methods in vitro, complementing the deeper depth penetration but lower resolution provided by PFC droplet imaging using in vivo medical imaging systems. In this work, we introduce a simple and robust method to miscibilize silica-coated nanoparticles into hydrophobic and lipophobic PFCs through fluorination of the silica surface via a hydrolysis-condensation reaction with 1H,1H,2H,2H-perfluorodecyltriethoxysilane. Using CdSe/ZnS core/shell QDs, we show that nanoscale, QD-labeled PFC droplets can be easily formed, with similar sizes and surface charges as unlabeled PFC droplets. The QD label can be used to determine the PFC droplet uptake into cells in vitro by fluorescence microscopy and flow cytometry, and can be used to validate the fate of PFC droplets in vivo in small animals via fluorescence microscopy of histological tissue sections. This is demonstrated in macrophage and cancer cells, and in rabbits, respectively. This work reveals the potential of using QD labels for rapid, preclinical, optical assessment of different PFC droplet formulations for their future use in patients.