Curci Debora, Lucafò Marianna, Parisse Pietro, Decorti Giuliana, Bramuzzo Matteo, Casalis Loredana, Stocco Gabriele
Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", 34137 Trieste, Italy.
Elettra Sincrotrone Trieste S.C.p.A., 34137 Trieste, Italy.
J Pers Med. 2022 Jun 10;12(6):948. doi: 10.3390/jpm12060948.
The use of infliximab has completely changed the therapeutic landscape in inflammatory bowel disease. However, despite its proven efficacy to induce and maintain clinical remission, increasing evidence suggests that treatment failure may be associated with inadequate drug blood concentrations. The introduction of biosensors based on different nanostructured materials for the rapid quantification of drugs has been proposed for therapeutic drug monitoring. This study aimed to apply atomic force microscopy (AFM)-based nanoassay for the measurement of infliximab concentration in serum samples of healthy donors and pediatric IBD patients. This assay measured the height signal variation of a nanostructured gold surface covered with a self-assembled monolayer of alkanethiols. Inside this monolayer, we embedded the DNA conjugated with a tumor necrosis factor able to recognize the drug. The system was initially fine-tuned by testing known infliximab concentrations (0, 20, 30, 40, and 50 nM) in buffer and then spiking the same concentrations of infliximab into the sera of healthy donors, followed by testing pediatric IBD patients. A good correlation between height variation and drug concentration was found in the buffer in both healthy donors and pediatric IBD patients (p-value < 0.05), demonstrating the promising use of AFM nanoassay in TDM.
英夫利昔单抗的使用彻底改变了炎症性肠病的治疗格局。然而，尽管其诱导和维持临床缓解的疗效已得到证实，但越来越多的证据表明，治疗失败可能与药物血药浓度不足有关。基于不同纳米结构材料的生物传感器已被提出用于治疗药物监测，以快速定量药物。本研究旨在应用基于原子力显微镜（AFM）的纳米检测法测量健康供体和儿童炎症性肠病（IBD）患者血清样本中的英夫利昔单抗浓度。该检测法测量了覆盖有烷硫醇自组装单分子层的纳米结构金表面的高度信号变化。在这个单分子层内部，我们嵌入了与能够识别该药物的肿瘤坏死因子偶联的DNA。该系统首先通过在缓冲液中测试已知浓度（0、20、30、40和50 nM）的英夫利昔单抗进行微调，然后将相同浓度的英夫利昔单抗加入健康供体的血清中进行测试，随后对儿童IBD患者进行测试。在健康供体和儿童IBD患者的缓冲液中，均发现高度变化与药物浓度之间具有良好的相关性（p值<0.05），这表明AFM纳米检测法在治疗药物监测中具有广阔的应用前景。
