Vascularized Tumor Spheroid-on-a-Chip Model Verifies Synergistic Vasoprotective and Chemotherapeutic Effects

Prolyl hydroxylases (PHD) inhibitors have been observed to improve drug distribution in mice tumors via blood vessel normalization, increasing the effectiveness of chemotherapy. These effects are yet to be demonstrated in human cell models. Tumor spheroids are three-dimensional cell clusters that ha...

Full description

Saved in:
Bibliographic Details
Published in:ACS biomaterials science & engineering 2022-03, Vol.8 (3), p.1215-1225
Main Authors: Hu, Zhiwei, Cao, Yuanxiong, Galan, Edgar A, Hao, Liang, Zhao, Haoran, Tang, Jiyuan, Sang, Gan, Wang, Hanqi, Xu, Bing, Ma, Shaohua
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Lab-On-A-Chip Devices
Mice
Neoplasms
Spheroids, Cellular
Tissue Engineering and Regenerative Medicine
Tumor Microenvironment
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Prolyl hydroxylases (PHD) inhibitors have been observed to improve drug distribution in mice tumors via blood vessel normalization, increasing the effectiveness of chemotherapy. These effects are yet to be demonstrated in human cell models. Tumor spheroids are three-dimensional cell clusters that have demonstrated great potential in drug evaluation for personalized medicine. Here, we used a perfusable vascularized tumor spheroid-on-a-chip to simulate the tumor microenvironment in vivo and demonstrated that the PHD inhibitor dimethylallyl glycine prevents the degradation of normal blood vessels while enhancing the efficacy of the anticancer drugs paclitaxel and cisplatin in human esophageal carcinoma (Eca-109) spheroids. Our results point to the potential of this model to evaluate anticancer drugs under more physiologically relevant conditions.
ISSN:2373-9878
2373-9878
DOI:10.1021/acsbiomaterials.1c01099