Alberto Kevin A, Hasna Begam M N, Xiong Hejian, Shinoda Wataru, Slesinger Paul A, Qin Zhenpeng, Nielsen Steven O
Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX 75080, USA.
Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
Nanoscale. 2025 Jan 23;17(4):2032-2042. doi: 10.1039/d4nr02509a.
Phospholipid based vesicles called liposomes are commonly used as packaging in advanced drug delivery applications. Stimuli-responsive liposomes have been designed to release their contents under certain conditions, for example through heating or illumination. However, in the case of photosensitive liposomes based on azo-PC, namely phosphatidylcholine lipids with azobenzene incorporated into one of the two lipid tails, the release mechanism is not known. Here we show, using fully-atomistic molecular dynamics simulations of pure azo-PC bilayers, that drug permeation through the bilayer is driven by a light-induced gel-to-liquid lipid phase transition that softens the membrane bending rigidity by an order of magnitude, increases the area per lipid, and decreases the membrane thickness. Furthermore, using phenol as a model drug, we quantified its translocation free energy and its ability to cross the bilayer as a result of a chemical potential gradient induced through a double-bilayer simulation unit cell. The molecular level structural and dynamic information obtained in this study should be of help in designing new azo-PC based liposomes.
被称为脂质体的基于磷脂的囊泡通常在先进的药物递送应用中用作包装材料。刺激响应性脂质体已被设计成在特定条件下释放其内容物，例如通过加热或光照。然而，对于基于偶氮磷脂酰胆碱（azo-PC）的光敏脂质体，即在两个脂质尾部之一中掺入偶氮苯的磷脂酰胆碱脂质，其释放机制尚不清楚。在这里，我们通过对纯偶氮磷脂酰胆碱双层进行全原子分子动力学模拟表明，药物通过双层的渗透是由光诱导的凝胶-液体脂质相变驱动的，该相变使膜弯曲刚度软化一个数量级，增加了每个脂质的面积，并减小了膜厚度。此外，我们以苯酚作为模型药物，通过双层模拟晶胞诱导的化学势梯度，量化了其转运自由能及其穿过双层的能力。本研究中获得的分子水平结构和动力学信息应有助于设计新型基于偶氮磷脂酰胆碱的脂质体。
