Polyglycerol-based Biomedical Matrix for Immunomagnetic Circulating Tumor Cell Isolation And Their Expansion into Tumor Spheroids for Drug Screening.

Circulating tumor cells (CTCs) have been established as distinct cancer biomarkers for diagnosis, as preclinical models, and therapeutic targets. Their use as preclinical models is limited owing to low purity after isolation and the lack of effective techniques to create 3D cultures that accurately mimic in-vivo conditions. Herein, we propose a two-component system for detecting, isolating, and expanding CTCs to generate multicellular tumor spheroids (MCTSs) that mimic the physiology and microenvironment of the diseased organ. First, we fabricated an anti-fouling biointerface on magnetic beads by adding a bioinert polymer layer and conjugation of biospecific ligands to isolate cancer cells, dramatically enhancing the selectivity and purity of the isolated cancer cells. Next, we encapsulated the isolated cells into self-degradable hydrogels synthesized using a thiol-click approach. The hydrogels were mechanochemically tuned to enable tumor spheroid growth to a size greater than 300 μm and to further release the grown spheroids while retaining their tumor-like characteristics. Additionally, drug treatment highlights the need for 3D culture environments rather than conventional 2D culture. The designed biomedical matrix shows potential as a universal method to ensure mimicry of in-vivo tumor characteristics in individual patients and to improve the predictability of preclinical screening of personalized therapeutics. This article is protected by copyright. All rights reserved.