Bis‐Boronic Acid Liposomes for Carbohydrate Recognition and Cellular Delivery
Bis‐Boronic Acid Liposomes for Carbohydrate Recognition and Cellular Delivery
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用于碳水化合物识别和细胞递送的双硼酸脂质体
DOI：
10.1002/cbic.202200402
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发表时间：
2022
期刊：
影响因子：
3.2
通讯作者：
Best, Michael D.
中科院分区：
文献类型：
--
作者：
Qualls, Megan L.;Hagewood, Hannah;Lou, Jinchao;Mattern‐Schain, Samuel I.;Zhang, Xiaoyu;Mountain, Deidra J.;Best, Michael D.
脂质体是有效的治疗性纳米载体，因为它们能够封装和增强多种药物和诊断剂的药代动力学特性。脂质体药物递送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至细胞。细胞膜聚糖为脂质体递送提供了令人兴奋的靶点，因为它们通常密集地聚集在细胞膜上，并且聚糖过量和异常的糖基化模式是患病细胞的共同特征。在此，我们报告了一种脂质体平台，该平台结合了双硼酸脂质（BBAL）以增加化合价，以实现选择性糖传感并增强基于碳水化合物结合相互作用的细胞表面识别。为了改变特性，设计并合成了多个在结合单元之间具有可变接头的 BBAL (1 a–d)。基于荧光的碳水化合物结合微孔板筛选表明，这些化合物根据其结构表现出不同的结合特性。此外，荧光显微镜实验表明，当 BBAL 掺入脂质体中时，细胞关联增强。这些结果表明，多价 BBAL 可作为一种令人兴奋的聚糖结合脂质体系统，用于靶向递送。
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.