摘要

The ability to measure drugs in the body rapidly and in real time would advance both our understanding of pharmacokinetics and our ability to optimally dose and deliver pharmacological therapies. To this end, we are developing electrochemical aptamer-based (E-AB) sensors, a seconds-resolved platform technology that, as critical for performing measurements in vivo, is reagentless, reversible, and selective enough to work when placed directly in bodily fluids. 
 


	
 


	Here we describe the development of an E-AB sensor against irinotecan, a member of the camptothecin family of cancer chemotherapeutics, and its adaptation to in vivo sensing. To achieve this we first re-engineered (via truncation) a previously reported DNA aptamer against the camptothecins to support high-gain E-AB signaling. We then co-deposited the modified aptamer with an unstructured, redox-reporter-modified DNA sequence whose output was independent of target concentration, rendering the sensor's signal gain a sufficiently strong function of square-wave frequency to support kinetic-differential-measurement drift correction. 
 


	
 


	The resultant, 200 μm-diameter, 3 mm-long sensor achieves 20 s-resolved, multi-hour measurements of plasma irinotecan when emplaced in the jugular veins of live rats, thus providing an unprecedentedly high-precision view into the pharmacokinetics of this class of chemotherapeutics.

译文

快速和实时测量体内药物的能力将提高我们对药代动力学的理解以及我们最佳剂量和药物治疗的能力。为此,我们正在开发基于电化学适体(E-AB)的传感器,这是一种秒级分辨率的平台技术,对于在体内进行测量至关重要,当直接将其放置在体液中时,它是无反应的、可逆的和有选择性的,足以工作。

本文介绍了喜树碱类抗癌药物伊立替康E-AB传感器的研制及其对体内传感的适应性。为了实现这一目标,我们首先重新设计(通过截短)一种先前报道的针对喜树碱的DNA适体,以支持高增益E-AB信号。然后,我们将修饰的适体与非结构的氧化还原报告修饰DNA序列共同沉积,其输出与目标浓度无关,从而使传感器的信号增益具有足够强的方波频率函数,以支持动态差分测量漂移校正。

这种直径200μm、长3 mm的传感器安置在活体大鼠颈静脉中,可实现20秒分辨率、多小时的血浆伊立替康测量,从而为这类化疗药物的药代动力学提供了前所未有的高精度视图。

Irinotecan

肿瘤 结肠癌 药物
概述  :  

伊立替康(Irinotecan,CPT-11)是细胞毒类药物家族中一员,属于喜树碱类新药物之一。喜树碱是一类含氮有机化合物,存在于动植物中,但主要集中于自然界植物中。喜树碱对中枢神经系统、心血管系统、免疫系统均有一定作用,同时还具有抗炎抗菌、抗病毒、保肝、杀虫以及抗肿瘤作用等。研究发现,多种生物碱都具有一定抗肿瘤活性,如喜树碱、紫杉醇等抗肿瘤药物已临床应用并取得一定效果。研究发现,生物碱可通过阻滞细胞周期发挥抗肿瘤作用。   喜树碱(Campt

Irinotecan 

释    义   n. 伊立替康(治疗结肠癌新药)

例    句   To evaluate the efficacy and toxicity of bortezomib with or without irinotecan, in patients with relapsed or refractory colorectal cancer (CRC). 评估复发或耐药结直肠癌单用硼替佐米或联合伊立替康的疗效和毒副作用。

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