The ability to exert control over lipid properties, including structure, charge, function, and self-assembly characteristics is a powerful tool that can be implemented to achieve a wide range of biomedical applications. Examples in this arena include the development of caged lipids for controlled activation of signaling properties, metabolic labeling strategies for tracking lipid biosynthesis, lipid activity probes for identifying cognate binding partners, approaches for in situ membrane assembly, and liposome triggered release strategies. In this Account, we describe recent advancements in the latter area entailing the development of stimuli-responsive liposomes through programmable changes to lipid self-assembly properties, which can be harnessed to drive the release of encapsulated contents toward applications including drug delivery. We will focus on an emerging paradigm involving liposomal platforms that are sensitized toward chemical agents ranging from metal cations to small organic molecules that exhibit dysregulation in disease states. This has been achieved by developing synthetic lipid switches that are designed to undergo programmed conformational changes upon the recognition of specific target analytes. These structural alterations are leveraged to perturb the packing of lipids within the membrane and thereby drive the release of encapsulated contents.

中文翻译：

---

采用由分子识别原理驱动的合成脂质开关的代谢物反应性脂质体

控制脂质特性（包括结构、电荷、功能​​和自组装特性）的能力是一种强大的工具，可以实现广泛的生物医学应用。这个领域的例子包括用于控制信号特性激活的笼状脂质的开发，用于跟踪脂质生物合成的代谢标记策略，用于识别同源结合伙伴的脂质活性探针，原位方法膜组装和脂质体触发释放策略。在这篇文章中，我们描述了后一领域的最新进展，即通过对脂质自组装特性的可编程改变来开发刺激反应性脂质体，这些特性可以用来推动封装内容物的释放，用于包括药物输送在内的应用。我们将关注一种新兴的范例，涉及脂质体平台，这些平台对从金属阳离子到在疾病状态下表现出失调的有机小分子等化学试剂敏感。这是通过开发合成脂质开关来实现的，这些脂质开关被设计为在识别特定目标分析物时进行程序化的构象变化。