Real-time, aptamer-based tracking of circulating therapeutic agents in living animals.
Real-time, aptamer-based tracking of circulating therapeutic agents in living animals.
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DOI：
10.1126/scitranslmed.3007095
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发表时间：
2013-11-27
影响因子：
17.1
通讯作者：
Soh HT
中科院分区：
文献类型：
--
作者：
Ferguson BS;Hoggarth DA;Maliniak D;Ploense K;White RJ;Woodward N;Hsieh K;Bonham AJ;Eisenstein M;Kippin TE;Plaxco KW;Soh HT
能够连续测量体内血流中特定分子的传感器将为临床医生提供一个了解患者健康及其对治疗反应的宝贵窗口。这种技术将实现真正的个性化医疗，其中治疗剂可以为每个患者定制最佳剂量，以最大限度地提高疗效并最大限度地减少副作用。不幸的是，连续的实时测量目前仅适用于少数目标，例如葡萄糖，乳糖和氧气，并且用于连续测量的少数现有平台无法推广用于监测其他分析物，例如小分子治疗剂。作为回应，我们开发了一种实时生物传感器，能够连续跟踪活体中广泛的循环药物。我们的用于体内连续监测（MEDIC）的微流控电化学检测器不需要外源试剂，在室温下工作，并且可以通过以模块化方式交换探针来重新配置以测量不同的目标分子。为了证明该系统的多功能性，我们测量了多柔比星（化疗药物）和卡那霉素（抗生素）在活体大鼠和人全血中的体内治疗浓度，持续数小时，具有亚分钟时间分辨率的高灵敏度和特异性。重要的是，我们表明MEDIC还可以实时获得单个动物的药代动力学参数。因此，正如连续葡萄糖监测技术目前正在彻底改变糖尿病护理一样，我们相信MEDIC可以通过直接检测生理参数来确保为个体患者提供最佳药物剂量，从而成为个性化医疗的有力推动者。
A sensor capable of continuously measuring specific molecules in the bloodstream in vivo would give clinicians a valuable window into patients’ health and their response to therapeutics. Such technology would enable truly personalized medicine, wherein therapeutic agents could be tailored with optimal doses for each patient to maximize efficacy and minimize side effects. Unfortunately, continuous, real-time measurement is currently only possible for a handful of targets, such as glucose, lactose, and oxygen, and the few existing platforms for continuous measurement are not generalizable for the monitoring of other analytes, such as small-molecule therapeutics. In response, we have developed a real-time biosensor capable of continuously tracking a wide range of circulating drugs in living subjects. Our microfluidic electrochemical detector for in vivo continuous monitoring (MEDIC) requires no exogenous reagents, operates at room temperature, and can be reconfigured to measure different target molecules by exchanging probes in a modular manner. To demonstrate the system's versatility, we measured therapeutic in vivo concentrations of doxorubicin (a chemotherapeutic) and kanamycin (an antibiotic) in live rats and in human whole blood for several hours with high sensitivity and specificity at sub-minute temporal resolution. Importantly, we show that MEDIC can also obtain pharmacokineticparameters for individual animals in real-time. Accordingly, just as continuous glucose monitoring technology is currently revolutionizing diabetes care, we believe MEDIC could be a powerful enabler for personalized medicine by ensuring delivery of optimal drug doses for individual patients based on direct detection of physiological parameters.
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影响因子：
--
作者：
Eikenberry, Steffen
通讯作者：
Eikenberry, Steffen
影响因子：
158.5
作者：
Keller, Till;Zeller, Tanja;Blankenberg, Stefan
通讯作者：
Blankenberg, Stefan
影响因子：
7.4
作者：
BAKER, DA;GOUGH, DA
通讯作者：
GOUGH, DA
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
--
作者：
Bauer, Jason W.;Petri, Michelle;Batliwalla, Franak M.;Koeuth, Thearith;Wilson, Joseph;Slattery, Catherine;Panoskaltsis-Mortari, Angela;Gregersen, Peter K.;Behrens, Timothy W.;Baechler, Emily C.
通讯作者：
Baechler, Emily C.