A Heart-Breast Cancer-on-a-Chip Platform for Disease Modeling and Monitoring of Cardiotoxicity Induced by Cancer Chemotherapy.
A Heart-Breast Cancer-on-a-Chip Platform for Disease Modeling and Monitoring of Cardiotoxicity Induced by Cancer Chemotherapy.
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DOI：
10.1002/smll.202004258
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发表时间：
2021-04
期刊：
影响因子：
--
通讯作者：
Shin SR
中科院分区：
文献类型：
--
作者：
Lee J;Mehrotra S;Zare-Eelanjegh E;Rodrigues RO;Akbarinejad A;Ge D;Amato L;Kiaee K;Fang Y;Rosenkranz A;Keung W;Mandal BB;Li RA;Zhang T;Lee H;Dokmeci MR;Zhang YS;Khademhosseini A;Shin SR
心脏毒性是癌症化疗最严重的副作用之一。目前监测化疗所致心脏毒性(CIC)的方法以及在体内或体外开发CIC平台的模型系统未能注意到CIC的早期迹象。此外，既往存在心脏功能障碍的乳腺癌(BC)患者可能会导致不同程度的CIC。在这里，我们提出了一个研究CIC的模型，在该模型中，不仅诱导的多能干细胞(IPSC)来源的心脏组织与BC组织在双器官平台上相互作用，而且电化学免疫适体传感器还可以监测细胞分泌的多个生物标志物。通过补充转化生长因子-β1促进IPSC来源的心脏组织的纤维化阶段，以评估阿霉素(DOX)治疗后健康和纤维化心脏组织的不同功能。使用免疫适体传感器评估的生物标记物的生产趋势与传统的酶联免疫吸附试验结果非常吻合，证明了我们的传感平台的准确性，具有更高的灵敏度和更低的检测下限，用于早期监测CIC和BC进展。此外，通过应用基于纳米颗粒的DOX递送系统，展示了该平台的多功能性。我们建议的平台可能有助于在未来早期发现和预测个别患者的CIC。本论文建立了一种心脏毒性芯片平台，该平台包含IPSC来源的心脏组织与乳腺癌组织的通讯，以及用于无创性监测细胞分泌多个生物标记物的电化学免疫适体传感器。所建议的平台能够区分化疗后健康和纤维化心脏组织的功能和毒性，从而有助于早期检测和预测个体患者的心脏毒性。
Cardiotoxicity is one of the most serious side effects of cancer chemotherapy. Current approaches to monitoring of chemotherapy-induced cardiotoxicity (CIC) as well as model systems that develop in vivo or in vitro CIC platforms fail to notice early signs of CIC. Moreover, breast cancer (BC) patients with preexisting cardiac dysfunctions may lead to different incident levels of CIC. Here, we present a model for investigating CIC where not only induced pluripotent stem cell (iPSC)-derived cardiac tissues are interacted with BC tissues on a dual-organ platform, but electrochemical immuno-Aptasensors can also monitor cell-secreted multiple biomarkers. Fibrotic stages of iPSC-derived cardiac tissues have been promoted with a supplement of transforming growth factor-β1 to assess the differential functionality in healthy and fibrotic cardiac tissues after treatment with doxorubicin (DOX). The production trend of biomarkers evaluated by using the immuno-Aptasensors well-matches the outcomes from conventional enzyme-linked immunosorbent assay, proving the accuracy of our sensing platform with much higher sensitivity and lower detection limits for early monitoring of CIC and BC progression. Furthermore, the versatility of this platform is demonstrated by applying a nanoparticle-based DOX-delivery system. Our proposed platform would potential help allow early detection and prediction of CIC in individual patients in the future. In this paper, a cardiotoxicity-on-a-chip platform containing iPSC-derived cardiac tissue communicated with breast cancer tissue and electrochemical immuno-Aptasensors for non-invasive monitoring of cell secreted multiple biomarkers. The suggested platform is capable of differentiating functionality and toxicity in healthy and fibrotic cardiac tissue after treatment with chemotherapy to step toward early detection and prediction of cardiotoxicity in individual patients.
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影响因子：
14
作者：
Nichol, Jason W.;Koshy, Sandeep T.;Bae, Hojae;Hwang, Chang M.;Yamanlar, Seda;Khademhosseini, Ali
通讯作者：
Khademhosseini, Ali
影响因子：
--
作者：
Eikenberry, Steffen
通讯作者：
Eikenberry, Steffen
DOI：
10.1155/2012/743193
发表时间：
2012
期刊：
Chemotherapy research and practice
影响因子：
--
作者：
Mitri Z;Constantine T;O'Regan R
通讯作者：
O'Regan R
影响因子：
4.3
作者：
Cox TR;Erler JT
通讯作者：
Erler JT
影响因子：
6.2
作者：
Henjes, F.;Bender, C.;von der Heyde, S.;Braun, L.;Mannsperger, H. A.;Schmidt, C.;Wiemann, S.;Hasmann, M.;Aulmann, S.;Beissbarth, T.;Korf, U.
通讯作者：
Korf, U.