Department of Materials Science and Engineering, Pennsylvania State University, 331 Steidle Building, University Park, State College, PA 16801, USA.
Molecules. 2023 Apr 20;28(8):3602. doi: 10.3390/molecules28083602.
Polymeric nanoparticles with reactive functional groups are an attractive platform for drug carriers that can be conjugated with drugs through a cleavable covalent linkage. Since the required functional groups vary depending on the drug molecule, there is a need for development of a novel post-modification method to introduce different functional groups to polymeric nanoparticles. We recently reported phenylboronic acid (PBA)-containing nanoparticles (BNP) with a unique framboidal morphology created via one-step aqueous dispersion polymerization. Since BNPs have high surface area due to their framboidal morphology and contain a high density of PBA groups, these particles can be used as nanocarriers for drugs that can bind to PBA groups such as curcumin and a catechol-bearing carbon monoxide donor. To further explore the potential of BNPs, in this article we report a novel strategy to introduce different functional groups to BNPs via the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction between the PBA groups and iodo- and bromo-coupling partners. We developed a new catalytic system that efficiently catalyzes Suzuki-Miyaura reactions in water without the need for an organic solvent, as confirmed by NMR. Using this catalyst system, we show that BNPs can be functionalized with carboxylic acids, aldehyde, and hydrazide groups while keeping their original framboidal morphology as confirmed via IR, alizarin red assay, and TEM. Furthermore, the potential of the functionalized BNP in drug delivery applications was demonstrated by conjugating the hydrogen sulfide (HS)-releasing compound anethole dithiolone to carboxylic acid-functionalized BNPs and show their HS-releasing capability in cell lysate.
具有反应性官能团的聚合物纳米粒子是一种有吸引力的药物载体平台，可通过可裂解的共价键与药物连接。由于所需的官能团取决于药物分子，因此需要开发新的后修饰方法将不同的官能团引入聚合物纳米粒子。我们最近报道了一种含有苯硼酸（PBA）的纳米粒子（BNP），其独特的准晶形态是通过一步水相分散聚合形成的。由于 BNPs 由于其准晶形态具有高的比表面积并且含有高密度的 PBA 基团，因此这些颗粒可用作可以与 PBA 基团结合的药物的纳米载体，例如姜黄素和含儿茶酚的一氧化碳供体。为了进一步探索 BNPs 的潜力，在本文中，我们报告了一种通过 PBA 基团与碘代和溴代偶联伙伴之间的钯催化 Suzuki-Miyaura 交叉偶联反应将不同官能团引入 BNPs 的新策略。我们开发了一种新的催化体系，该体系在无需有机溶剂的情况下即可在水中有效地催化 Suzuki-Miyaura 反应，这通过 NMR 得到了证实。使用该催化剂体系，我们证明 BNPs 可以被羧酸、醛和酰肼官能化，同时保持其原始的准晶形态，这通过 IR、茜素红测定和 TEM 得到了证实。此外，通过将释放硫化氢（HS）的化合物茴香二硫酮与羧酸官能化的 BNPs 缀合，证明了功能化的 BNP 在药物传递应用中的潜力，并在细胞裂解物中显示出其 HS 释放能力。
