National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou, 310014, China.
Hangzhou Push-Kang Biotechnology Co., Ltd, Zhejiang, China.
Colloids Surf B Biointerfaces. 2019 Sep 1;181:872-878. doi: 10.1016/j.colsurfb.2019.06.035. Epub 2019 Jun 17.
Fluorescence imaging is widely used to determine biodistribution of drugs in mice. However, the dye distribution may not be able to exactly reflect the true distribution of drug molecules. We synthesized PTX-Cy5.5 and mPEG-PLA-Cy5.5, and then prepared dye-loaded nanoparticles (NPs) (Cy5.5, DiR, PTX-Cy5.5, and mPEG-PLA-Cy5.5), dye and PTX co-loaded NPs, and PTX-loaded NPs, respectively. The particle sizes of resulting NPs were between 42.7 nm and 68.8 nm, and Zeta potential was between -0.86 mV and -8.49 mV. The biodistribution of fluorescent NPs (dye-loaded NPs and dye and PTX co-loaded NPs) on Bel-7402 tumor-bearing mice was studied via in vivo fluorescence imaging assays, results of which suggested that Cy5.5 loaded NPs and Cy5.5 conjugates (PTX-Cy5.5 and mPEG-PLA-Cy5.5) formulated NPs can reflect the tissue distribution of PTX whether it was incorporated or not. However, DiR failed to reflect true tissue distribution of PTX unless it was co-loaded with PTX. Based on these results, a guidance for the selection of dyes in drug distribution investigations and disease-targeted treatment was presented.
荧光成像是广泛用于确定药物在小鼠体内的生物分布的方法。然而，染料的分布可能无法准确反映药物分子的真实分布。我们合成了 PTX-Cy5.5 和 mPEG-PLA-Cy5.5，然后制备了负载染料的纳米颗粒（NPs）（Cy5.5、DiR、PTX-Cy5.5 和 mPEG-PLA-Cy5.5）、染料和 PTX 共载 NPs 和 PTX 载 NPs。所得 NPs 的粒径在 42.7nm 至 68.8nm 之间，Zeta 电位在-0.86mV 至-8.49mV 之间。通过体内荧光成像试验研究了荧光 NPs（负载染料的 NPs 和负载染料和 PTX 的 NPs）在 Bel-7402 荷瘤小鼠体内的分布，结果表明，无论是否掺入，Cy5.5 负载的 NPs 和 Cy5.5 缀合物（PTX-Cy5.5 和 mPEG-PLA-Cy5.5）形成的 NPs 都可以反映 PTX 的组织分布。然而，除非与 PTX 共载，否则 DiR 无法反映 PTX 的真实组织分布。基于这些结果，为药物分布研究和疾病靶向治疗中染料的选择提供了指导。
