High Throughput Confined Migration Microfluidic Device for Drug Screening

作者全名："Yang, Zihan; Zhou, Zhihang; Si, Tongxu; Zhou, Zhengdong; Zhou, Li; Chin, Y. Rebecca; Zhang, Liang; Guan, Xinyuan; Yang, Mengsu"

作者地址："[Yang, Zihan; Zhou, Zhihang; Si, Tongxu; Zhou, Zhengdong; Zhou, Li; Chin, Y. Rebecca; Zhang, Liang; Yang, Mengsu] City Univ Hong Kong, Dept Biomed Sci, Kowloon, 83 Tat Chee Ave, Hong Kong 999077, Peoples R China; [Yang, Zihan; Zhou, Zhihang; Si, Tongxu; Zhou, Zhengdong; Zhou, Li; Chin, Y. Rebecca; Zhang, Liang; Yang, Mengsu] City Univ Hong Kong, Tung Biomed Sci Ctr, Kowloon, 83 Tat Chee Ave, Hong Kong 999077, Peoples R China; [Yang, Zihan; Si, Tongxu; Zhou, Zhengdong; Yang, Mengsu] City Univ Hong Kong, Futian Res Inst, Dept Precis Diagnost & Therapeut Technol, Shenzhen 518000, Guangdong, Peoples R China; [Zhou, Zhihang; Zhou, Zhengdong] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing 400010, Peoples R China; [Guan, Xinyuan] Univ Hong Kong, Dept Clin Oncol, Hong Kong 999077, Peoples R China"

通信作者："Yang, MS (通讯作者)，City Univ Hong Kong, Dept Biomed Sci, Kowloon, 83 Tat Chee Ave, Hong Kong 999077, Peoples R China.; Yang, MS (通讯作者)，City Univ Hong Kong, Tung Biomed Sci Ctr, Kowloon, 83 Tat Chee Ave, Hong Kong 999077, Peoples R China.; Yang, MS (通讯作者)，City Univ Hong Kong, Futian Res Inst, Dept Precis Diagnost & Therapeut Technol, Shenzhen 518000, Guangdong, Peoples R China."

来源：SMALL

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000912637200001

JCR分区：Q1

影响因子：13

年份：2023

卷号：19

期号：16

开始页：　

结束页：　

文献类型：Article

关键词：cancer metastasis; confined migration; drug screening; microfluidics

摘要："Cancer metastasis is the major cause of cancer-related death. Excessive extracellular matrix deposition and increased stiffness are typical features of solid tumors, creating confined spaces for tumor cell migration and metastasis. Confined migration is involved in all metastasis steps. However, confined and unconfined migration inhibitors are different and drugs available to inhibit confined migration are rare. The main challenges are the modeling of confined migration, the suffering of low throughput, and others. Microfluidic device has the advantage to reduce reagent consumption and enhance throughput. Here, a microfluidic chip that can achieve multi-function drug screening against the collective migration of cancer cells under confined environment is designed. This device is applied to screen out effective drugs on confined migration among a novel mechanoreceptors compound library (166 compounds) in hepatocellular carcinoma, non-small lung cancer, breast cancer, and pancreatic ductal adenocarcinoma cells. Three compounds that can significantly inhibit confined migration in pan-cancer: mitochonic acid 5 (MA-5), SB-705498, and diphenyleneiodonium chloride are found. Finally, it is elucidated that these drugs targeted mitochondria, actin polymerization, and cell viability, respectively. In sum, a high-throughput microfluidic platform for screening drugs targeting confined migration is established and three novel inhibitors of confined migration in multiple cancer types are identified."

基金机构："HetaoShenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Shenzhen Park Project [HZQB-KCZYZ-2021017]; Hong Kong Research Grant Council [CityU_11319516, R1020-18F]; Hong Kong Innovation and Technology Fund [MRP/045/21X]; National Key Research and Development Program of China [2018YFA0901100/2018YFA0901104]; City University of Hong Kong [9678223]; National Natural Science Fund of China [81972285]; Natural Science Foundation of Chongqing [2022NSCQ-MSX1038]; Senior Medical Talents Program of Chongqing for Young and Middle-aged and Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University [13-004-009]"

基金资助正文："Z.Y. and Z.Z. contributed equally to this work. M.Y. gratefully acknowledges funding support by a grant from HetaoShenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Shenzhen Park Project (HZQB-KCZYZ-2021017), Hong Kong Research Grant Council (CityU_11319516 and R1020-18F), the Hong Kong Innovation and Technology Fund (MRP/045/21X), the National Key Research and Development Program of China (2018YFA0901100/2018YFA0901104), City University of Hong Kong (Project #9678223), the National Natural Science Fund of China (No. 81972285), the Natural Science Foundation of Chongqing (2022NSCQ-MSX1038), Senior Medical Talents Program of Chongqing for Young and Middle-aged and Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University (13-004-009)."