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基于聚(苯胺-co-4-氨基苯甲酸-绿色合成的铟纳米粒子)平台的拉帕替尼(一种乳腺癌药物)新型细胞色素 P450-3A4 酶纳米生物传感器的研制。

Novel Cytochrome P450-3A4 Enzymatic Nanobiosensor for Lapatinib (a Breast Cancer Drug) Developed on a Poly(anilino-co-4-aminobenzoic Acid-Green-Synthesised Indium Nanoparticle) Platform.

机构信息

SensorLab (UWC Sensor Laboratories), University of the Western Cape, Private Bag X17, Bellville, Cape Town 7535, South Africa.

Nanotechnology Innovation Centre, Advanced Materials Division, Mintek, Private Bag X3015, Randburg, Johannesburg 2125, South Africa.

出版信息

Biosensors (Basel). 2023 Sep 21;13(9):897. doi: 10.3390/bios13090897.

Abstract

Breast cancer (BC) is one of the most common types of cancer disease worldwide and it accounts for thousands of deaths annually. Lapatinib is among the preferred drugs for the treatment of breast cancer. Possible drug toxicity effects of lapatinib can be controlled by real-time determination of the appropriate dose for a patient at the point of care. In this study, a novel highly sensitive polymeric nanobiosensor for lapatinib is presented. A composite of poly(anilino-co-4-aminobenzoic acid) co-polymer {poly(ANI-co-4-ABA)} and coffee extract-based green-synthesized indium nanoparticles (InNPs) was used to develop the sensor platform on a screen-printed carbon electrode (SPCE), i.e., SPCE||poly(ANI-co-4-ABA-InNPs). Cytochrome P450-3A4 (CYP3A4) enzyme and polyethylene glycol (PEG) were incorporated on the modified platform to produce the SPCE||poly(ANI-co-4-ABA-InNPs)|CYP3A4|PEG lapatinib nanobiosensor. Experiments for the determination of the electrochemical response characteristics of the nanobiosensor were performed with cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The nanobiosensor calibration for 0-100 ng/mL lapatinib was linear and gave limit of detection (LOD) values of 13.21 ng/mL lapatinib and 18.6 ng/mL lapatinib in physiological buffer and human serum, respectively. The LOD values are much lower than the peak plasma concentration (C) of lapatinib (2.43 µg/mL), which is attained 4 h after the administration of a daily dose of 1250 mg lapatinib. The electrochemical nanobiosensor also exhibited excellent anti-interference performance and stability.

摘要

乳腺癌(BC)是全球最常见的癌症类型之一,每年导致数千人死亡。拉帕替尼是治疗乳腺癌的首选药物之一。通过在护理点实时确定患者的适当剂量,可以控制拉帕替尼的潜在药物毒性作用。在这项研究中,提出了一种新型的用于拉帕替尼的高灵敏度聚合物纳米生物传感器。聚(苯胺-共-4-氨基苯甲酸)共聚物{聚(ANI-co-4-ABA)}和基于咖啡提取物的绿色合成铟纳米粒子(InNPs)的复合材料被用于在丝网印刷碳电极(SPCE)上开发传感器平台,即 SPCE||poly(ANI-co-4-ABA-InNPs)。细胞色素 P450-3A4(CYP3A4)酶和聚乙二醇(PEG)被掺入修饰后的平台上,以产生 SPCE||poly(ANI-co-4-ABA-InNPs)|CYP3A4|PEG 拉帕替尼纳米生物传感器。使用循环伏安法(CV)和差分脉冲伏安法(DPV)进行了确定纳米生物传感器电化学响应特征的实验。纳米生物传感器对 0-100ng/mL 拉帕替尼的校准是线性的,在生理缓冲液和人血清中分别给出了 13.21ng/mL 拉帕替尼和 18.6ng/mL 拉帕替尼的检测限(LOD)值。LOD 值远低于拉帕替尼的峰值血浆浓度(C)(2.43μg/mL),这是在每天服用 1250mg 拉帕替尼 4 小时后达到的。电化学纳米生物传感器还表现出出色的抗干扰性能和稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b74/10527071/640275b7b3aa/biosensors-13-00897-sch001.jpg

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