Details

Autor(en) / Beteiligte

• Agarwal, Pranay
• Wang, Hai
• Sun, Mingrui
• Xu, Jiangsheng
• Zhao, Shuting
• Liu, Zhenguo
• Gooch, Keith J
• Zhao, Yi
• Lu, Xiongbin
• He, Xiaoming

Titel

Microfluidics Enabled Bottom-Up Engineering of 3D Vascularized Tumor for Drug Discovery

Ist Teil von

• ACS nano, 2017-07, Vol.11 (7), p.6691-6702

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2017

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Development of high-fidelity three-dimensional (3D) models to recapitulate the tumor microenvironment is essential for studying tumor biology and discovering anticancer drugs. Here we report a method to engineer the 3D microenvironment of human tumors, by encapsulating cancer cells in the core of microcapsules with a hydrogel shell for miniaturized 3D culture to obtain avascular microtumors first. The microtumors are then used as the building blocks for assembling with endothelial cells and other stromal cells to create macroscale 3D vascularized tumor. Cells in the engineered 3D microenvironment can yield significantly larger tumors in vivo than 2D-cultured cancer cells. Furthermore, the 3D vascularized tumors are 4.7 and 139.5 times more resistant to doxorubicin hydrochloride (a commonly used chemotherapy drug) than avascular microtumors and 2D-cultured cancer cells, respectively. Moreover, this high drug resistance of the 3D vascularized tumors can be overcome by using nanoparticle-mediated drug delivery. The high-fidelity 3D tumor model may be valuable for studying the effect of microenvironment on tumor progression, invasion, and metastasis and for developing effective therapeutic strategy to fight against cancer.