Fluorescence‐Guided Spatial Drug Screening in 3D Colorectal Cancer Spheroids

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Fluorescence‐Guided Spatial Drug Screening in 3D Colorectal Cancer Spheroids
Title:
Fluorescence‐Guided Spatial Drug Screening in 3D Colorectal Cancer Spheroids
Journal Title:
Advanced Healthcare Materials
Keywords:
Publication Date:
22 May 2024
Citation:
Yau, J. N. N., Yempala, T., Muthuramalingam, R. P. K., Giustarini, G., Teng, G., Ang, W. H., Gibson, D., Adriani, G., & Pastorin, G. (2024). Fluorescence‐Guided Spatial Drug Screening in 3D Colorectal Cancer Spheroids. Advanced Healthcare Materials. Portico. https://doi.org/10.1002/adhm.202400203
Abstract:
AbstractThe limited recapitulation of critical cancer features in 2D cultures causes poor translatability of preclinical results from in vitro assays to in vivo tumor models. This contributes to slow drug development with a low success rate. 3D cultures better recapitulate the tumor microenvironment, enabling more accurate predictions when screening drug candidates and improving the development of chemotherapeutics. Platinum (Pt) (IV) compounds are promising prodrugs designed to reduce the severe systemic toxicity of widely used Food and Drug Administration (FDA)‐approved Pt(II) drugs such as cisplatin. Here, this work presents spatiotemporal evaluations in 3D colorectal cancer (CRC) spheroids of mitochondria‐targeting Pt(IV) complexes. CRC spheroids provide a greater pathophysiological recapitulation of in vivo tumors than 2D cultures by a marked upregulation of the ABCG2 chemoresistance marker expression. Furthermore, new 3D‐staining protocols are introduced to evaluate the real‐time decrease in mitochondria membrane potential (ΔΨ) in CRC spheroids, and a Pt‐sensing dye to quantify the Pt mitochondrial accumulation. Finally, this work demonstrates a correlation between in vitro results and the efficacy of the compounds in vivo. Overall, the CRC spheroids represent a fast and cost‐effective model to assess the behavior of Pt compounds in vitro and predict their translational potential in CRC treatment.
License type:
Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
Funding Info:
This research / project is supported by the National University of Singapore (NUS) - NanoNash Program
Grant Reference no. : A-0004336-00-00

This research / project is supported by the Ministry of Education (MOE) - Tier 1
Grant Reference no. : A-0008504-00-00

This research / project is supported by the Agency for Science, Technology and Research (A*STAR) - GAP funding
Grant Reference no. : A-8001819-00-00

This research / project is supported by the Ministry of Education (MOE) - AcRF Tier 2
Grant Reference no. : T2EP30122-0027

This work was funded by 1) Singapore Immunology Network (SIgN) 2) Biomedical Research Council (BMRC),, A*STAR 3) NAMIC grant (grant number A-8001601-00-00)
Description:
ISSN:
2192-2659
2192-2640