Lou Jinchao, Carr Adam J, Watson Alexa J, Mattern-Schain Samuel I, Best Michael D
Department of Chemistry, University of Tennessee, 1420 Circle Drive, Knoxville, TN, 37996, USA.
Chemistry. 2018 Mar 7;24(14):3599-3607. doi: 10.1002/chem.201705810. Epub 2018 Feb 8.
Liposomal drug delivery would benefit from enhanced control over content release. Here, we report a novel avenue for triggering release driven by chemical composition using liposomes sensitized to calcium-a target chosen due to its key roles in biology and disease. To demonstrate this principle, we synthesized calcium-responsive lipid switch 1, designed to undergo conformational changes upon calcium binding. The conformational change perturbs membrane integrity, thereby promoting cargo release. This was shown through fluorescence-based release assays via dose-dependent response depending on the percentage of 1 in liposomes, with minimal background leakage in controls. DLS experiments indicated dramatic changes in particle size upon treatment of liposomes containing 1 with calcium. In a comparison of ten naturally occurring metal cations, calcium provided the greatest release. Finally, STEM images showed significant changes in liposome morphology upon treatment of liposomes containing 1 with calcium. These results showcase lipid switches driven by molecular recognition principles as an exciting avenue for controlling membrane properties.
脂质体药物递送将受益于对内容物释放的增强控制。在此，我们报告了一种由化学成分驱动触发释放的新途径，使用对钙敏感的脂质体——选择钙作为靶点是因为其在生物学和疾病中起关键作用。为了证明这一原理，我们合成了钙响应脂质开关1，其设计为在结合钙时发生构象变化。构象变化扰乱膜的完整性，从而促进货物释放。通过基于荧光的释放测定法，根据脂质体中1的百分比呈剂量依赖性反应显示了这一点，对照中的背景泄漏最小。动态光散射实验表明，用钙处理含有1的脂质体后，粒径发生了显著变化。在对十种天然存在的金属阳离子的比较中，钙提供了最大的释放量。最后，扫描透射电子显微镜图像显示，用钙处理含有1的脂质体后，脂质体形态发生了显著变化。这些结果表明，由分子识别原理驱动的脂质开关是控制膜性质的一个令人兴奋的途径。
