3D collagen microchamber arrays for combined chemotherapy effect evaluation on cancer cell numbers and migration

Jingru Yao; Guoqiang Li; Lianjie Zhou; Shuyan Xu; Kena Song; Hongfei Zhang; Xianquan Zhang; Jianwei Shuai; Fangfu Ye; Ming Li; Guo Chen; He Liu; Peter Shaw; Liyu Liu

doi:10.1063/5.0121952

3D collagen microchamber arrays for combined chemotherapy effect evaluation on cancer cell numbers and migration

Biomicrofluidics. 2023 Jan 3;17(1):014101. doi: 10.1063/5.0121952. eCollection 2023 Jan.

Authors

Jingru Yao¹, Guoqiang Li², Lianjie Zhou¹, Shuyan Xu¹, Kena Song³, Hongfei Zhang⁴, Xianquan Zhang⁴, Jianwei Shuai, Fangfu Ye, Ming Li⁵, Guo Chen¹, He Liu⁶, Peter Shaw⁶, Liyu Liu¹

Affiliations

¹ Chongqing Key Laboratory of Soft Condensed Matter Physics and Smart Materials, College of Physics, Chongqing University, Chongqing 401331, China.
² Chongqing Key Laboratory of Environmental Materials and Remediation Technologies, College of Chemistry and Environmental Engineering (Chongqing University of Arts and Sciences), Chongqing 402160, People's Republic of China.
³ College of Medical Technology and Engineering, Henan University of Science and Technology, Henan 471023, China.
⁴ Hygeia International Cancer Hospital, Chongqing 401331, China.
⁵ Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
⁶ Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Wenzhou, Zhejiang 325000, China.

Abstract

Breast cancer metastasis involves complex mechanisms, particularly when patients are undergoing chemotherapy. In tissues, tumor cells encounter cell-cell interactions, cell-microenvironment interactions, complex nutrient, and drug gradients. Currently, two-dimensional cell culture systems and animal models are challenging to observe and analyze cell responses to microenvironments with various physical and bio-chemical conditions, and microfluidic technology has been systematically developed to address this dilemma. In this study, we have constructed a combined chemotherapy evaluation chip (CCEC) based on microfluidic technology. The chip possesses 192 diamond-shaped microchambers containing MDA-MB-231-RFP cells, and each microchamber is composed of collagen to mimic breast cancer and its surrounding microenvironment. In addition, by adding medium containing different drugs to the medium channels of CCEC, composite drug (paclitaxel+gemcitabine+7rh and paclitaxel+fluorouracil+PP2) concentration gradients, and single drug (paclitaxel, gemcitabine, 7rh, fluorouracil, PP2) concentration gradients have been established in the five collagen regions, respectively, so that each localized microchamber in the regions has a unique drug microenvironment. In this way, we evaluated the composite and single chemotherapy efficacy on the same chip by statistically analyzing their effects on the numbers and migration of the cell. The quantitative results in CCECs reveal that the inhibition effects on the numbers and migration of MDA-MB-231-RFP cell under the composite drug gradients are more optimal than those of the single drugs. Besides, the cancer cell inhibition effect between the groups composed of two drugs has also been compared, that is the paclitaxel+gemcitabine, paclitaxel+fluorouracil, and paclitaxel+PP2 have better cell numbers and migration inhibition effects than paclitaxel+7rh. The results indicate that the bio-mimetic and high-throughput combined chemotherapy evaluation platform can serve as a more efficient and accurate tool for preclinical drug development and screening.