DiMartini Emily T, Lowe Christopher J, Shreiber David I
Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
J Funct Biomater. 2023 Mar 14;14(3):153. doi: 10.3390/jfb14030153.
Stimuli-responsive biomaterials are an emerging strategy that leverage common pathophysiological triggers to target drug delivery to limit or avoid toxic side effects. Native free radicals, such as reactive oxygen species (ROS), are widely upregulated in many pathological states. We have previously demonstrated that native ROS are capable of crosslinking and immobilizing acrylated polyethylene glycol diacrylate (PEGDA) networks and coupled payloads in tissue mimics, providing evidence for a potential targeting mechanism. To build on these promising results, we evaluated PEG dialkenes and dithiols as alternative polymer chemistries for targeting. The reactivity, toxicity, crosslinking kinetics, and immobilization potential of PEG dialkenes and dithiols were characterized. Both the alkene and thiol chemistries crosslinked in the presence of ROS, generating high molecular weight polymer networks that immobilized fluorescent payloads in tissue mimics. Thiols were especially reactive and even reacted with acrylates in the absence of free radicals, and this motivated us to explore a two-phase targeting approach. Delivering thiolated payloads in a second phase, after the initial polymer net formation, allowed greater control over the payload dosing and timing. Two-phase delivery combined with a library of radical-sensitive chemistries can enhance the versatility and flexibility of this free radical-initiated platform delivery system.
刺激响应性生物材料是一种新兴策略，它利用常见的病理生理触发因素来靶向给药，以限制或避免毒副作用。天然自由基，如活性氧（ROS），在许多病理状态下会广泛上调。我们之前已经证明，天然ROS能够使丙烯酸化聚乙二醇二丙烯酸酯（PEGDA）网络和偶联的负载在组织模拟物中交联并固定，为潜在的靶向机制提供了证据。为了基于这些有前景的结果进一步研究，我们评估了聚乙二醇二烯烃和二硫醇作为靶向的替代聚合物化学物质。对聚乙二醇二烯烃和二硫醇的反应性、毒性、交联动力学和固定潜力进行了表征。烯烃和硫醇化学物质在ROS存在下都会交联，生成高分子量聚合物网络，将荧光负载固定在组织模拟物中。硫醇特别具有反应性，甚至在没有自由基的情况下也能与丙烯酸酯反应，这促使我们探索一种两相靶向方法。在初始聚合物网络形成后，在第二阶段递送硫醇化负载，可以更好地控制负载剂量和时间。两相递送与一系列对自由基敏感的化学物质相结合，可以增强这种自由基引发的平台递送系统的多功能性和灵活性。
