Calcium-Responsive Liposomes via a Synthetic Lipid Switch
Calcium-Responsive Liposomes via a Synthetic Lipid Switch
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DOI：
10.1002/chem.201705810
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发表时间：
2018-03-07
影响因子：
4.3
通讯作者：
Best, Michael D.
中科院分区：
文献类型：
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作者：
Lou, Jinchao;Carr, Adam J.;Best, Michael D.
脂质体药物递送将受益于对内容物释放的增强控制。在这里，我们报告了一种新的途径，触发释放驱动的化学成分使用脂质体致敏钙-一个目标选择，由于其在生物学和疾病的关键作用。为了证明这一原理，我们合成了钙响应性脂质开关1，其被设计为在钙结合时经历构象变化。构象变化扰乱膜完整性，从而促进货物释放。这通过基于荧光的释放测定通过依赖于1在脂质体中的百分比的剂量依赖性响应显示，在对照中具有最小的背景泄漏。DLS实验表明，在用钙处理含有1的脂质体后，粒径发生了显著变化。在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。最后，STEM图像显示在用钙处理含有1的脂质体后脂质体形态的显著变化。这些结果展示了由分子识别原理驱动的脂质开关作为控制膜特性的令人兴奋的途径。
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 calciuma-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.