光开关脂质，特别是偶氮苯衍生的磷脂酰胆碱 (azoPC) 脂质，提供了一种独特的机制，可在暴露于紫外线 (UV) 辐射时可逆地改变膜特性。通过全原子分子动力学模拟，我们探讨了紫外线照射诱导的 AzoPC 脂质的反式光异构化 (TCPI) 如何影响脂质膜的结构和动力学，该脂质膜由二棕榈酰磷脂酰胆碱 (DPPC) 和与其成分相似的胆固醇组成。 DOXIL® 的。  对膜的两种状态“暗”状态（含有顺式偶氮 PC 脂质）和“亮”状态（含有 85% 顺式偶氮 PC 和 15% 反式偶氮 PC 脂质）的结构和动力学分析表明 TCPI 降低了膜堆积密度并增加脂质的扩散性。我们已经证明，与“暗”状态相比，在膜的“亮”状态下，抗癌药物阿霉素（DOX）的嵌入增强。这项研究阐明了脂质成分、光开关和脂质-药物相互作用之间复杂的相互作用，有助于设计用于靶向药物输送和生物医学应用的基于脂质的系统。© 2024 Wiley‐VCH GmbH。

Photoswitchable lipids, particularly azobenzene-derivatized phosphatidylcholine (azoPC) lipids, offer a unique mechanism for reversible modification of membrane properties upon exposure to ultraviolet (UV) radiation. Through all-atom molecular dynamics simulations, we explore how UV irradiation-induced trans-to-cis photoisomerization(TCPI) of AzoPC lipid influences the structure and dynamics of a lipid membrane, composed of dipalmitoylphosphatidylcholine (DPPC) and cholesterol with similar composition to that of the DOXIL®.  Structural and dynamical analyses of two states of the membrane, 'dark' state (containing cis-azoPC lipid) and 'bright' state (containing 85% cis-azoPC and 15% trans-azoPC lipids) reveal that the TCPI reduces membrane packing density and increases diffusivity of lipids. We have demonstrated an enhanced intercalation of doxorubicine (DOX), an anticancer drug, in the 'bright' state of the membrane compared to that in 'dark' state. This study - elucidating the complex interplay between lipid composition, photoswitching, and lipid-drug interactions - contribute to the design of lipid-based systems for targeted drug delivery and biomedical applications.© 2024 Wiley‐VCH GmbH.