Detection of selective androgen receptor modulators (SARMs) in serum using a molecularly imprinted nanoparticle surface plasmon resonance sensor
Detection of selective androgen receptor modulators (SARMs) in serum using a molecularly imprinted nanoparticle surface plasmon resonance sensor
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DOI：
10.1039/d2tb00270a
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发表时间：
2022-06-06
影响因子：
7
通讯作者：
Turner, Nicholas W.
中科院分区：
文献类型：
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作者：
Henderson, Alisha;Sullivan, Mark, V;Turner, Nicholas W.
选择性雄激素受体调节剂（SARM）是一类作用于雄激素受体的相当新的治疗化合物。他们提供类似的合成代谢类固醇的属性，但与一个大大减少雄激素配置文件。它们已成为竞技体育中普遍滥用的物质。由于相对较新，检测系统仅限于色谱法。在这里，我们提出了一种针对三种常用SARMS Andarine、Ligandrol和RAD-140的表面等离子体共振传感器，使用高亲和力分子印迹纳米颗粒（nanoMIPs）作为识别元件。合成的nanoMIPS对于安达林、Ligandrol和RAD-140 nanoMIPS分别表现出29.3 nM、52.5 nM和75.1 nM的解离常数（K-D）值。使用替代SARM探索颗粒的交叉反应性，其中nanoMIP表现出良好的特异性。使用胎牛血清（FBS）来评估基于SPR的nanoMIP传感器检测可比较的生物基质中的目标化合物的能力，Andarine、Ligandrol和RAD-140 nanoMIP的观察到的K-D值分别为12.3 nM、31.9 nM和28.1 nM。根据FBS中的校准图估计理论检测限（LoD），结果表明基于nanoMIP的传感器在理论上有可能在低至亚nM范围内测量这些SARM。重要的是，这些水平低于世界反兴奋剂机构为这些化合物设定的最低要求性能限值（MRPL）。这项研究强调了现代分子印迹的力量，以快速解决所需的分子识别新的化合物的利益。
Selective Androgen Receptor Modulators (SARMs) are a fairly new class of therapeutic compounds that act upon the androgen receptor. They proffer similar anabolic properties to steroids, but with a much-reduced androgenic profile. They have become a popular substance of abuse in competitive sport. Being relatively new, detection systems are limited to chromatographic methods. Here we present a surface plasmon resonance sensor for three commonly-used SARMS, Andarine, Ligandrol and RAD-140, using high-affinity molecularly imprinted nanoparticles (nanoMIPs) as the recognition element. Synthesised nanoMIPS exhibited dissociation constant (K-D) values of 29.3 nM, 52.5 nM and 75.1 nM for Andarine, Ligandrol and RAD-140 nanoMIPs, respectively. Cross-reactivity of the particles was explored using the alternative SARMs, with the nanoMIPs demonstrating good specificity. Fetal Bovine Serum (FBS) was used to assess the ability of the SPR-based nanoMIP sensor to detect the target compounds in a comparable biological matrix, with observed K-D values of 12.3 nM, 31.9 nM and 28.1 nM for Andarine, Ligandrol and RAD-140 nanoMIPs, respectively. Theoretical limits of detection (LoD) were estimated from a calibration plot in FBS and show that the nanoMIP-based sensors have the potential to theoretically measure these SARMs in the low to sub nM range. Crucially these levels are below the minimum required performance limit (MRPL) set for these compounds by WADA. This study highlights the power of modern molecular imprinting to rapidly address required molecular recognition for new compounds of interest.