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.
Pranay Agarwal†‡#, Hai Wang†‡§#, Mingrui Sun†‡, Jiangsheng Xu†‡§, Shuting Zhao†‡, Zhenguo Liu‡∥, Keith J. Gooch†‡, Yi Zhao†, Xiongbin Lu⊥, and Xiaoming He*†‡§
†Department of Biomedical Engineering, ‡Dorothy M. Davis Heart and Lung Research Institute, §Comprehensive Cancer Center, and ∥Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio 43210, United States
⊥ Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States
ACS Nano, Article ASAP
Publication Date (Web): June 14, 2017
Copyright © 2017 American Chemical Society