Department of Chemistry, University of Tennessee, 1420 Circle Drive, Knoxville, TN, 37996, USA.
Department of Surgery, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway, Knoxville, TN 37920, USA.
Chembiochem. 2022 Nov 4;23(21):e202200402. doi: 10.1002/cbic.202200402. Epub 2022 Sep 21.
Liposomes are effective therapeutic nanocarriers due to their ability to encapsulate and enhance the pharmacokinetic properties of a wide range of drugs and diagnostic agents. A primary area in which improvement is needed for liposomal drug delivery is to maximize the delivery of these nanocarriers to cells. Cell membrane glycans provide exciting targets for liposomal delivery since they are often densely clustered on cell membranes and glycan overabundance and aberrant glycosylation patterns are a common feature of diseased cells. Herein, we report a liposome platform incorporating bis-boronic acid lipids (BBALs) to increase valency in order to achieve selective saccharide sensing and enhance cell surface recognition based on carbohydrate binding interactions. In order to vary properties, multiple BBALs (1 a-d) with variable linkers in between the binding units were designed and synthesized. Fluorescence-based microplate screening of carbohydrate binding showed that these compounds exhibit varying binding properties depending on their structures. Additionally, fluorescence microscopy experiments indicated enhancements in cellular association when BBALs were incorporated within liposomes. These results demonstrate that multivalent BBALs serve as an exciting glycan binding liposome system for targeted delivery.
脂质体由于能够包裹并增强各种药物和诊断试剂的药代动力学特性，因此是有效的治疗性纳米载体。脂质体药物递送中需要改进的一个主要领域是最大限度地将这些纳米载体递送到细胞中。细胞膜糖提供了脂质体递送的令人兴奋的靶标，因为它们通常在细胞膜上密集聚集，并且糖过量和异常糖基化模式是病变细胞的常见特征。在这里，我们报告了一种包含双硼酸脂（BBAL）的脂质体平台，以增加价数，从而实现基于碳水化合物结合相互作用的选择性糖感应和增强细胞表面识别。为了改变性质，设计并合成了多个具有结合单元之间可变连接子的 BBAL（1a-d）。基于荧光的微孔板筛选碳水化合物结合表明，这些化合物的结构不同，其结合性质也不同。此外，荧光显微镜实验表明，当 BBAL 被包含在脂质体中时，细胞的结合得到增强。这些结果表明，多价 BBAL 是一种用于靶向递药的令人兴奋的糖结合脂质体系统。
