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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用于控制释放抗癌药物的还原响应分子印迹聚（2-异丙烯基-2-恶唑啉）。


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有趣，因为细胞内的还原应力高于血流中的还原应力，从而提供了细胞摄取后概念性的控制释放机制。在这项工作中，我们报道了使用 3,3'-二硫代二丙酸 (DTDPA) 作为基于聚(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) 的合成还原响应功能交联剂。 DTDPA 的二硫键可通过添加三(2-羧乙基)膦 (TCEP) 裂解，从而导致还原诱导的 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种不同的动力学模型，从而表明不同的吸附机制。释放动力学表明，TCEP 的添加显着影响 PiPOx-MIP 中 5-FU 的释放，而对于非印迹 PiPOx，没有观察到统计学上的相关差异。这项工作为分子印迹 PiPOx 还原诱导的 5-FU 释放提供了概念基础，在未来的工作中可能会进一步开发成 MIP 纳米颗粒，用于治疗药物的控制释放。