Institute of Functional Nano & Soft Materials, Laboratory (FUNSOM) and Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, PR China.
Small. 2014 Mar 26;10(6):1125-32. doi: 10.1002/smll.201302230. Epub 2013 Dec 9.
A new strategy is presented for using doped small-molecule organic nanoparticles (NPs) to achieve high-performance fluorescent probes with strong brightness, large Stokes shifts and tunable emissions for in vitro and in vivo imaging. The host organic NPs are used not only as carriers to encapsulate different doped dyes, but also as fluorescence resonance energy transfer donors to couple with the doped dyes (as acceptors) to achieve multicolor luminescence with amplified emissions (AE). The resulting optimum green emitting NPs show high brightness with quantum yield (QY) of up to 45% and AE of 12 times; and the red emitting NPs show QY of 14% and AE of 10 times. These highly-luminescent doped NPs can be further surface modified with poly(maleic anhydride-alt-1-octadecene)-polyethylene glycol (C18PMH-PEG), endowing them with excellent water dispersibility and robust stability in various bio-environments covering wide pH values from 2 to 10. In this study, cytotoxicity studies and folic acid targeted cellular imaging of these multicolor probes are carried out to demonstrate their potential for in vitro imaging. On this basis, applications of the NP probes in in vivo and ex vivo imaging are also investigated. Intense fluorescent signals of the doped NPs are distinctly, selectively and spatially resolved in tumor sites with high sensitivity, due to the preferential accumulation of the NPs in tumor sites through the passive enhanced permeability and retention effect. The results clearly indicate that these doped NPs are promising fluorescent probes for biomedical applications.
提出了一种新策略，即利用掺杂小分子有机纳米粒子（NPs）来实现具有高亮度、大斯托克斯位移和可调发射的高性能荧光探针，用于体外和体内成像。所使用的主体有机 NPs 不仅作为载体来封装不同的掺杂染料，而且还作为荧光共振能量转移供体与掺杂染料（作为受体）耦合，以实现具有放大发射（AE）的多色发光。所得最佳绿色发射 NPs 表现出高亮度，量子产率（QY）高达 45%，AE 为 12 倍；红色发射 NPs 的 QY 为 14%，AE 为 10 倍。这些高发光掺杂 NPs 可以进一步用马来酸酐-alt-1-十八烯-聚乙二醇（C18PMH-PEG）进行表面修饰，赋予它们在从 2 到 10 的宽 pH 值范围内具有优异的水分散性和在各种生物环境中的强稳定性。在这项研究中，进行了这些多色探针的细胞毒性研究和叶酸靶向细胞成像，以证明它们在体外成像中的潜力。在此基础上，还研究了 NP 探针在体内和离体成像中的应用。由于 NPs 通过被动增强的渗透性和保留效应优先积聚在肿瘤部位，因此在肿瘤部位可以明显、选择性和空间分辨地获得掺杂 NPs 的强烈荧光信号，具有高灵敏度。结果清楚地表明，这些掺杂 NPs 是用于生物医学应用的有前途的荧光探针。
