Controllable gelation of artificial extracellular matrix for altering mass transport and improving cancer therapies

Di-Wei Zheng, Sheng Hong, Qiu-Ling Zhang, Xue Dong, Pei Pan, Wen-Fang Song, Wen Song, Si-Xue Cheng and Xian-Zheng Zhang ()
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Di-Wei Zheng: Wuhan University
Sheng Hong: Wuhan University
Qiu-Ling Zhang: Wuhan University
Xue Dong: Wuhan University
Pei Pan: Wuhan University
Wen-Fang Song: Wuhan University
Wen Song: Wuhan University
Si-Xue Cheng: Wuhan University
Xian-Zheng Zhang: Wuhan University

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Global alterations in the metabolic network provide substances and energy to support tumor progression. To fuel these metabolic processes, extracellular matrix (ECM) plays a dominant role in supporting the mass transport and providing essential nutrients. Here, we report a fibrinogen and thrombin based coagulation system to construct an artificial ECM (aECM) for selectively cutting-off the tumor metabolic flux. Once a micro-wound is induced, a cascaded gelation of aECM can be triggered to besiege the tumor. Studies on cell behaviors and metabolomics reveal that aECM cuts off the mass transport and leads to a tumor specific starvation to inhibit tumor growth. In orthotopic and spontaneous murine tumor models, this physical barrier also hinders cancer cells from distant metastasis. The in vivo gelation provides an efficient approach to selectively alter the tumor mass transport. This strategy results in a 77% suppression of tumor growth. Most importantly, the gelation of aECM can be induced by clinical operations such as ultrasonic treatment, surgery or radiotherapy, implying this strategy is potential to be translated into a clinical combination regimen.

Date: 2020
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DOI: 10.1038/s41467-020-18493-7

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