Buyens Kevin, Lucas Bart, Raemdonck Koen, Braeckmans Kevin, Vercammen Jo, Hendrix Jelle, Engelborghs Yves, De Smedt Stefaan C, Sanders Niek N
Laboratory of General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
J Control Release. 2008 Feb 18;126(1):67-76. doi: 10.1016/j.jconrel.2007.10.024. Epub 2007 Nov 7.
SiRNA based therapeutics are currently under investigation for treatment of cancer and viral infections. Upon intravenous administration, the nanoscopic delivery systems which carry the siRNA need to be stable in serum, an aspect which is often overlooked in numerous publications on siRNA delivery systems. Techniques currently available for studying the dissociation of siRNA-liposome complexes are time consuming and incompatible with full serum. We therefore developed a fluorescence fluctuation spectroscopy (FFS) based method which allows to monitor the integrity of siRNA-carrier complexes. The method can very rapidly provide quantitative information on the complex integrity in biological media, like full human serum, and at very low siRNA concentrations (approximately 20 nM siRNA). Information on the integrity of intravenously injected siRNA nanoparticles in serum is crucial. Consequently, the FFS method reported in this work may find broad applicability in the field of siRNA-carrier design.
基于小干扰RNA（siRNA）的疗法目前正在用于癌症和病毒感染治疗的研究中。静脉给药时，携带siRNA的纳米递送系统需要在血清中保持稳定，而这一方面在众多关于siRNA递送系统的出版物中常常被忽视。目前可用于研究siRNA-脂质体复合物解离的技术既耗时又与全血清不相容。因此，我们开发了一种基于荧光涨落光谱（FFS）的方法，该方法能够监测siRNA-载体复合物的完整性。该方法可以非常快速地提供有关生物介质（如全人血清）中复合物完整性的定量信息，且所需的siRNA浓度非常低（约20 nM siRNA）。血清中静脉注射的siRNA纳米颗粒完整性的信息至关重要。因此，本文报道的FFS方法可能在siRNA-载体设计领域具有广泛的适用性。
