Integrated Systems Laboratory - EPFL - École Polytechnique Fédérale de Lausanne, Switzerland.
CNR-IPCF (Rome) and Department of Physics - Parma University - Parma, Italy.
Biosens Bioelectron. 2011 May 15;26(9):3914-9. doi: 10.1016/j.bios.2011.03.009. Epub 2011 Mar 17.
This work focuses on P450 biosensors based on multiwalled carbon nanotubes (MWCNT) and different cytochrome isoforms: 3A4, 2B4, 2C9. The proposed biosensors exhibit enhanced sensitivities and decreased detection limits thanks to carbon nanotubes. The MWCNT structuring improves the sensitivity from 5.1 to 20.5 nA/mM mm(2) in case of CYP2B4-mediated Benzphetamine detection, from 0.26 to 0.63 nA/μM mm(2) in case of CYP3A4-mediated Cyclophosphamide detection, and from 0.11 to 0.25 nA/μM mm(2) in case of CYP2C9-mediated Naproxen detection. By using MWCNT, the limit of detection was enhanced from 59 to 12 μM in case of Cyclophosphamide and from to 187 to 82 μM in case of Naproxen. This makes possible the drug detection in human serum within the pharmacological range. In the paper, a new mathematical model is also proposed to succeed in discriminating different drug contributions in a mixture containing both Cyclophosphamide and Dextromethorphan or combining Naproxen and Flurbiprofen. Data analysis shows variations in reduction peaks that are dependent on the drug ratio, and that are consistent with competitive kinetics of substrates. This new approach enables multiple drug detection and opens the way to possible applications in personalized therapy.
这项工作专注于基于多壁碳纳米管 (MWCNT) 和不同细胞色素同工酶的 P450 生物传感器：3A4、2B4、2C9。由于碳纳米管的存在，所提出的生物传感器表现出更高的灵敏度和更低的检测限。在苯丙胺检测中，MWCNT 的结构将 CYP2B4 介导的灵敏度从 5.1 提高到 20.5 nA/mM mm(2)，在环磷酰胺检测中，将 CYP3A4 介导的灵敏度从 0.26 提高到 0.63 nA/μM mm(2)，在萘普生检测中，将 CYP2C9 介导的灵敏度从 0.11 提高到 0.25 nA/μM mm(2)。通过使用 MWCNT，环磷酰胺的检测限从 59 μM 提高到 12 μM，萘普生的检测限从 187 μM 提高到 82 μM。这使得在药理学范围内能够检测人血清中的药物。在本文中，还提出了一种新的数学模型，成功地在含有环磷酰胺和右美沙芬或组合萘普生和氟比洛芬的混合物中区分不同药物的贡献。数据分析表明还原峰的变化取决于药物的比例，并且与底物的竞争动力学一致。这种新方法能够实现多种药物的检测，并为个性化治疗中的可能应用开辟了道路。
