Analysis of chemosensitivity of tumor spheroids exposed to two-dimensional gradient of combination drugs in a hydrogel-based diffusion microfluidic platform.

Autor: Lei KF; Department of Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan; Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Electrical & Electronic Engineering, Yonsei University, Seoul, South Korea. Electronic address: kflei@mail.cgu.edu.tw., Lin YT; Department of Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan., Boreddy SKR; Department of Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan., Pai PC; Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou, Taiwan.
Jazyk: angličtina
Zdroj: Analytica chimica acta [Anal Chim Acta] 2024 Dec 15; Vol. 1332, pp. 343371. Date of Electronic Publication: 2024 Oct 24.
DOI: 10.1016/j.aca.2024.343371
Abstrakt: Background: Liver cancer stands as a leading cause of cancer-related deaths globally, challenging conventional treatments due to resistance to chemotherapy and targeted therapy. Although frontline medications show initial efficacy, prolonged use often leads to resistance and harm. Current clinical strategies rely on combination therapies, but evaluating their effectiveness remains challenging.
Results: To address this, we developed a hydrogel-based diffusion microfluidic platform for assessing chemosensitivity. This platform features a hydrogel-filled diffusion layer linked to liquid wells, allowing the creation of drug gradients. Tumor spheroids, cultured on the non-adhesive hydrogel surface, were exposed to single or combination drug gradients. Analysis revealed that drug efficacy, quantified by IC 50 values, could be determined from responses to single drug gradients. A novel method was introduced to assess spheroid circularity as a time-invariant index of drug efficacy. Furthermore, exposing spheroids to 2D combination drug gradients allowed intuitive visualization of their responses via a color map. This analysis identified optimal drug combinations, exhibiting superior efficacy to monotherapy.
Significance: The microfluidic platform enables assessment of synergistic effects and replicates in vivo conditions, enhancing the relevance of test results. By offering a streamlined, fast, and efficient drug screening approach, this platform aims to provide insight into tumor spheroid responses to varying drug combinations, facilitating more effective clinical applications.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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