The Chemistry of Boronic Acids in Nanomaterials for Drug Delivery.

作者：A. Stubelius, Sangeun Lee, A. Almutairi · 发表于：Accounts of Chemical Research · 年份：2019 · DOI：10.1021/acs.accounts.9b00292 · 被引用次数：215 · 研究领域：Chemistry、Medicine

Interest in increasing drug delivery efficiency has risen over the past decade both as a means to improve efficacy of already clinically available drugs and due to the increased difficulties of approving new drugs. As a functional group for targeted drug delivery, boronic acids (BAs) have been incorporated in polymeric particles both as a stimuli-responsive functional group and as a targeting ligand. Here, BA chemistry presents a wealth of opportunities for biological applications. It not only reacts with several chemical markers of disease such as reactive oxygen species (ROS), adenosine triphosphate (ATP), glucose, and reduced pH, but it also acts as ligands for diols such as sialic acid. These stimuli-responsive drug delivery systems optimize delivery of therapeutics based on rational design and precise molecular engineering. When designing materials containing BA, the unique chemical properties are important to take into consideration such as its vacant p-orbital, its molecular geometry, and the designed acid's pKa. Instead of behaving as most carboxylic acids that donate protons, BAs instead primarily act as Lewis acids that accept electrons. In aqueous solution, most polymers containing BA exist in an equilibrium between their triangular hydrophobic form and a tetrahedral hydrophilic form. The most common pKa's are in the nonphysiological range of 8-10, and much ongoing research focuses on modifying BAs into materials sensitive to a more physiologically relevant pH rang...