Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals.
Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals.
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DOI：
10.1126/sciadv.abk2901
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发表时间：
2022-01-07
期刊：
影响因子：
13.6
通讯作者：
Soh HT
中科院分区：
文献类型：
--
作者：
Seo JW;Fu K;Correa S;Eisenstein M;Appel EA;Soh HT
展示了一种可以在活体啮齿动物模型中连续监测多个肿瘤部位体内药物水平的生物传感器。化疗方案的有效性和安全性从根本上取决于其药代动力学。目前这是根据血液样本进行测量的，但肿瘤微环境的异常脉管系统和生理异质性可能会产生与体循环截然不同的药物药代动力学。我们开发了一种植入式微电极阵列传感器，可以通过同时测量多个部位的瘤内药代动力学来收集此类基于组织的药代动力学数据。我们使用金纳米多孔微电极，即使在反复组织植入和长期暴露于肿瘤微环境后，也能保持强大的传感器性能。我们证明了在啮齿动物模型中连续体内监测化疗药物阿霉素在多个肿瘤部位的浓度，并证明了相对于循环的药代动力学的明显差异，这可能对药物功效和安全性产生有意义的影响。该平台可能对癌症治疗的临床前体内表征有价值，并可能为未来的临床应用奠定基础。
A biosensor that can continuously monitor drug levels in vivo at multiple tumor sites in a live rodent model is demonstrated. The efficacy and safety of a chemotherapy regimen fundamentally depends on its pharmacokinetics. This is currently measured based on blood samples, but the abnormal vasculature and physiological heterogeneity of the tumor microenvironment can produce radically different drug pharmacokinetics relative to the systemic circulation. We have developed an implantable microelectrode array sensor that can collect such tissue-based pharmacokinetic data by simultaneously measuring intratumoral pharmacokinetics from multiple sites. We use gold nanoporous microelectrodes that maintain robust sensor performance even after repeated tissue implantation and extended exposure to the tumor microenvironment. We demonstrate continuous in vivo monitoring of concentrations of the chemotherapy drug doxorubicin at multiple tumor sites in a rodent model and demonstrate clear differences in pharmacokinetics relative to the circulation that could meaningfully affect drug efficacy and safety. This platform could prove valuable for preclinical in vivo characterization of cancer therapeutics and may offer a foundation for future clinical applications.
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影响因子：
38.3
作者：
Liu J;Fu TM;Cheng Z;Hong G;Zhou T;Jin L;Duvvuri M;Jiang Z;Kruskal P;Xie C;Suo Z;Fang Y;Lieber CM
通讯作者：
Lieber CM
DOI：
10.1016/j.jconrel.2013.09.013
发表时间：
2013-12-28
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Ernsting MJ;Murakami M;Roy A;Li SD
通讯作者：
Li SD
影响因子：
3.5
作者：
Lu, WL;Qi, XR;Wei, SL
通讯作者：
Wei, SL
影响因子：
7.4
作者：
Arroyo-Curras, Netzahualcoyotl;Scida, Karen;Plaxco, Kevin W.
通讯作者：
Plaxco, Kevin W.
影响因子：
8.4
作者：
Idili, Andrea;Arroyo-Curras, Netzahualcoyotl;Plaxco, Kevin W.
通讯作者：
Plaxco, Kevin W.