Department of Chemistry, University of Tennessee, 1420 Circle Drive, Knoxville, TN, 37996, USA.
Chemistry. 2022 Aug 10;28(45):e202201164. doi: 10.1002/chem.202201164. Epub 2022 Jul 6.
Liposomes are effective therapeutic delivery nanocarriers due to their ability to encapsulate and enhance the pharmacokinetic properties of a wide range of therapeutics. Two primary areas in which improvement is needed for liposomal drug delivery is to enhance the ability to infiltrate cells and to facilitate derivatization of the liposome surface. Herein, we report a liposome platform incorporating a cyclic disulfide lipid (CDL) for the dual purpose of enhancing cell entry and functionalizing the liposome membrane through thiol-disulfide exchange. In order to accomplish this, CDL-1 and CDL-2, composed of lipoic acid (LA) or asparagusic acid (AA) appended to a lipid scaffold, were designed and synthesized. A fluorescence-based microplate immobilization assay was implemented to show that these compounds enable convenient membrane decoration through reaction with thiol-functionalized small molecules. Additionally, fluorescence microscopy experiments indicated dramatic enhancements in cellular delivery when CDLs were incorporated within liposomes. These results demonstrate that multifunctional CDLs serve as an exciting liposome system for surface decoration and enhanced cellular delivery.
脂质体由于能够包裹和增强多种治疗药物的药代动力学特性，因此是有效的治疗性递药纳米载体。脂质体药物递送需要改进的两个主要领域是增强细胞渗透能力和促进脂质体表面的衍生化。在此，我们报告了一种包含环二硫键脂质（CDL）的脂质体平台，其具有增强细胞进入和通过巯基-二硫键交换功能化脂质体膜的双重目的。为了实现这一点，设计并合成了由脂酰基（LA）或天门冬氨酸（AA）连接到脂质支架上的 CDL-1 和 CDL-2。实施了基于荧光的微孔板固定化测定法，以表明这些化合物可以通过与巯基化的小分子反应来方便地进行膜修饰。此外，荧光显微镜实验表明，当将 CDL 掺入脂质体中时，细胞内递药显著增强。这些结果表明，多功能 CDL 是一种令人兴奋的脂质体系统，可用于表面修饰和增强细胞递药。
