Chen Hongtao, Kim Sungwon, He Wei, Wang Haifeng, Low Philip S, Park Kinam, Cheng Ji-Xin
Department of Chemistry, Weldon School of Biomedical Engineering, and Oncological Sciences Center, Purdue University, West Lafayette, Indiana 47907, USA.
Langmuir. 2008 May 20;24(10):5213-7. doi: 10.1021/la703570m. Epub 2008 Feb 8.
Understanding the in vivo behavior of nanoparticles is critical for the translation of nanomedicine from laboratory research to clinical trials. In this work, in vivo Forster resonance energy transfer (FRET) imaging was employed to monitor the release of hydrophobic molecules from circulating poly(ethylene glycol)-poly( D, L-lactic acid) (PEG-PDLLA) micelles. A lipophilic FRET pair (DiIC(18) and DiOC(18)) was physically entrapped into micelle cores by mimicking the loading of hydrophobic drugs. The FRET efficiency was found significantly reduced within 15 min after intravenous injection, implying that DiIC(18) and DiOC(18) quickly escaped from the circulating micelles. FRET spectroscopy studies further demonstrated that alpha- and beta-globulins were major factors for the observed fast release, while gamma-globulins, albumin, and red blood cells played minor roles. These results provide useful information for developing blood-stable micelles to deliver hydrophobic drugs to the target site via prolonged circulation and extravasation from the vascular system.
了解纳米颗粒的体内行为对于将纳米医学从实验室研究转化为临床试验至关重要。在这项工作中，采用体内Förster共振能量转移（FRET）成像来监测循环聚（乙二醇）-聚（D，L-乳酸）（PEG-PDLLA）胶束中疏水分子的释放。通过模拟疏水性药物的负载，将亲脂性FRET对（DiIC(18)和DiOC(18)）物理包裹在胶束核心中。发现在静脉注射后15分钟内FRET效率显著降低，这意味着DiIC(18)和DiOC(18)迅速从循环胶束中逸出。FRET光谱研究进一步表明，α-球蛋白和β-球蛋白是观察到的快速释放的主要因素，而γ-球蛋白、白蛋白和红细胞起次要作用。这些结果为开发血液稳定的胶束提供了有用信息，以便通过延长循环和从血管系统渗出将疏水性药物递送至靶位点。
