Laboratoire de Conception et Application de Molécules Bioactives, UMR 7199 CNRS-Université de Strasbourg, Faculté de Pharmacie, 67401 Illkirch Cedex, France.
Biomaterials. 2010 Jun;31(17):4781-8. doi: 10.1016/j.biomaterials.2010.02.047. Epub 2010 Mar 29.
In this study, the ability of synthetic fluorinated lipospermines to bind DNA and siRNA was investigated and the transfection efficiency and toxicity of the resulting lipoplexes in cell lines were evaluated. Three lipopolyamines displaying fluorous tags close to their cationic polar head ("HFP" polyamines) were synthesized. Their ability to condense pDNA and siRNA, and to form nanoparticles were characterized. Lipoplex stability was investigated in the presence of different surface active compounds and was shown to be significantly improved due to the presence of the fluorous tags. Transfection efficiencies were studied in HepG2 and 911 cell lines, and compared to that of DOGS, DOTAP, and Lipofectamine 2000. Also, the ability of these compounds to deliver nucleic acids into cells in the presence of high concentration of serum was quantified. By incorporating two fluorous tags in the direct vicinity of the polycationic head group of the lipospermines, we show efficient pDNA and siRNA formulation, and delivery to cultured cells. Fluorinated lipoplexes exhibit improved stability in the presence of amphiphilic compounds and retain high transfection efficiency in the presence of 50-75% serum. These results demonstrate that lipospermines displaying fluorous tags close to their cationic polar head bind to and deliver pDNA and siRNA with high cell viability in different cell lines. They are efficient non-viral vectors that exhibit remarkable serum compatibility.
在这项研究中，研究了合成的氟化脂多胺与 DNA 和 siRNA 结合的能力，并评估了由此形成的脂质体在细胞系中的转染效率和毒性。合成了三种带有靠近阳离子极性头的氟标记的脂多胺（“HFP”多胺）。研究了它们凝聚 pDNA 和 siRNA 的能力以及形成纳米颗粒的能力。研究了脂质体在不同表面活性剂存在下的稳定性，并发现由于氟标记的存在，其稳定性得到了显著提高。在 HepG2 和 911 细胞系中研究了转染效率，并与 DOGS、DOTAP 和 Lipofectamine 2000 进行了比较。此外，还定量研究了这些化合物在高浓度血清存在下将核酸递送到细胞中的能力。通过将两个氟标记物整合到脂多胺的聚阳离子头基团的直接附近，我们展示了高效的 pDNA 和 siRNA 制剂和向培养细胞的递送。氟化物脂质体在两性化合物存在下表现出更好的稳定性，并在存在 50-75%血清的情况下保持高转染效率。这些结果表明，带有靠近阳离子极性头的氟标记的脂多胺与 pDNA 和 siRNA 结合，并在不同细胞系中以高细胞活力递送 pDNA 和 siRNA。它们是高效的非病毒载体，具有显著的血清相容性。
