Piergentili Irene, Bouwmans Pepijn R, Reinalda Luuk, Lewis Reece W, Klemm Benjamin, Liu Huanhuan, de Kruijff Robin M, Denkova Antonia G, Eelkema Rienk
Delft University of Technology, Department of Chemical Engineering Van der Maasweg 9 2629 HZ Delft The Netherlands
Delft University of Technology, Department of Radiation Science and Technology Mekelweg 15 2629 JB Delft The Netherlands.
Polym Chem. 2022 Mar 30;13(16):2383-2390. doi: 10.1039/d2py00207h. eCollection 2022 Apr 19.
In certain tumor and diseased tissues, reactive oxygen species (ROS), such as HO, are produced in higher concentrations than in healthy cells. Drug delivery and release systems that respond selectively to the presence of ROS, while maintaining their stability in "healthy" biological conditions, have great potential as on-site therapeutics. This study presents polymer micelles with 4-(methylthio)phenyl ester functionalities as a ROS-responsive reactivity switch. Oxidation of the thioether moieties triggers ester hydrolysis, exposing a hydrophylic carboxylate and leading to micellar disassembly. At 37 °C, the micelles fall apart on a timescale of days in the presence of 2 mM HO and within hours at higher concentrations of HO (60-600 mM). In the same time frame, the nanocarriers show no hydrolysis in oxidant-free physiological or mildly acidic conditions. This logic gate cascade behavior represents a step forward to realize drug delivery materials capable of selective response to a biomarker input.
在某些肿瘤和患病组织中，活性氧（ROS），如羟基自由基（HO）的产生浓度高于健康细胞。能够在“健康”生物条件下保持稳定性的同时对ROS的存在做出选择性响应的药物递送和释放系统，作为现场治疗手段具有巨大潜力。本研究展示了具有4-（甲硫基）苯基酯官能团的聚合物胶束作为一种ROS响应性反应开关。硫醚部分的氧化触发酯水解，暴露出亲水性羧酸盐并导致胶束解体。在37℃下，在2 mM羟基自由基存在的情况下，胶束在数天内分解，而在更高浓度的羟基自由基（60 - 600 mM）下，数小时内就会分解。在相同的时间范围内，纳米载体在无氧化剂的生理或轻度酸性条件下不发生水解。这种逻辑门级联行为代表了在实现能够对生物标志物输入做出选择性响应的药物递送材料方面向前迈进了一步。
