Trigger-responsive materials are capable of controlled drug release in the presence of a specific trigger. Reduction induced drug release is especially interesting as the reductive stress is higher inside cells than in the bloodstream, providing a conceptual controlled release mechanism after cellular uptake. In this work, we report the synthesis of 5-fluorouracil (5-FU) molecularly imprinted polymers (MIPs) based on poly(2-isopropenyl-2-oxazoline) (PiPOx) using 3,3′-dithiodipropionic acid (DTDPA) as a reduction-responsive functional cross-linker. The disulfide bond of DTDPA can be cleaved by the addition of tris(2-carboxyethyl)phosphine (TCEP), leading to a reduction-induced 5-FU release. Adsorption isotherms and kinetics for 5-FU indicate that the adsorption kinetics process for imprinted and non-imprinted adsorbents follows two different kinetic models, thus suggesting that different mechanisms are responsible for adsorption. The release kinetics revealed that the addition of TCEP significantly influenced the release of 5-FU from PiPOx-MIP, whereas for non-imprinted PiPOx, no statistically relevant differences were observed. This work provides a conceptual basis for reduction-induced 5-FU release from molecularly imprinted PiPOx, which in future work may be further developed into MIP nanoparticles for the controlled release of therapeutic agents.

中文翻译：

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还原响应分子印迹聚（2-异丙烯基-2-恶唑啉），用于控制释放的抗癌药。

触发响应材料能够在特定触发条件下控制药物释放。还原诱导的药物释放特别令人感兴趣，因为细胞内部的还原应力高于血液中的应力，从而在细胞摄取后提供了概念性的控释机制。在这项工作中，我们报告了使用3,3'-二硫代二丙酸（DTDPA）作为聚（2-异丙烯基-2-恶唑啉）（PiPOx）的5-氟尿嘧啶（5-FU）分子印迹聚合物（MIP）的合成还原反应性功能交联剂。DTDPA的二硫键可通过添加三（2-羧乙基）膦（TCEP）裂解，导致还原诱导的5-FU释放。5-FU的吸附等温线和动力学表明，印迹和非印迹吸附剂的吸附动力学过程遵循两个不同的动力学模型，因此表明吸附的机理不同。释放动力学表明，TCEP的添加显着影响了PiFUx-MIP中5-FU的释放，而对于非印迹PiPOx，未观察到统计学上的相关差异。这项工作为还原诱导的5-FU从分子印迹PiPOx的释放提供了概念基础，在将来的工作中，它可能会进一步发展成用于控制药物释放的MIP纳米颗粒。释放动力学表明，TCEP的添加显着影响了PiFUx-MIP中5-FU的释放，而对于非印迹PiPOx，未观察到统计学上的相关差异。这项工作为还原诱导的5-FU从分子印迹PiPOx的释放提供了概念基础，在将来的工作中，它可能会进一步发展成用于控制药物释放的MIP纳米颗粒。释放动力学表明，TCEP的添加显着影响了PiFUx-MIP中5-FU的释放，而对于非印迹PiPOx，未观察到统计学上的相关差异。这项工作为还原诱导的5-FU从分子印迹PiPOx的释放提供了概念基础，在将来的工作中，它可能会进一步发展成用于控制药物释放的MIP纳米颗粒。