Multifunctional Hybrid Magnetic Microgel Synthesis for Immune-Based Isolation and Post-Isolation Culture of Tumor Cells

Abstract

Circulating tumor cells are of utmost importance among various biomarkers in liquid biopsies as a prognosis indicator of metastasis as well as in chemotherapeutic monitoring. This study introduces an efficient tool composed of soft nano/hybrid immune microgels for magnetic isolation of targeted tumor cells. The development process involves the in situ synthesis of magnetic nanoparticles within the three-dimensional matrix of thermoresponsive microgels. Surface modification and anti-EpCAM conjugation are adjusted by changing the temperature, and a conjugation efficiency of around 70% is achieved by using a protein G linker. Anti-EpCAM-conjugated nano/hybrid magnetic microgels are used to isolate EpCAM-expressing breast adenocarcinoma MCF-7 cells from culture media and whole blood with an efficiency of 75 and 70%, respectively. Furthermore, we demonstrate the ability of the hybrid microgels to isolate cancer cells with a purity of 65% and culture the cells post-isolation for further drug studies. The multifunctional hybrid microcarriers reported in this work can be potentially used for continuous monitoring of cancers and in personalized medicine.

Review on the advancements of magnetic gels: towards multifunctional magnetic liposome-hydrogel composites for biomedical applications

“…Considering the discussed properties of the hydrogel component, magnetic gels can also be fabricated as magnetic nanogels [186,187], microgels [188][189][190], and macrogels [181,191]. Further, other modalities can be introduced, for instance, through the use of magnetic/plasmonic nanoparticles (plasmonic magnetogels) [24].…”

Rheology Applied to Microgels: Brief (Revision of the) State of the Art

“…MIPs are polymeric matrices with specific cavities for molecular recognition. An example of these systems can be found in the work done by Seyfoori et al in which hybrid immune microgels are developed as a tool for the magnetic isolation of targeted tumor cells [ 57 ]. These circulating tumor cells are of extreme relevance for biopsies as an indicator of metastasis.…”

Magnetic response of CoFe2O4 nanoparticles confined in a PNIPAM microgel network

“…For example the MNPs bind covalently to the polymer network 37,38 or non-covalently by embedding MNPs into brushes 39 or microgels. 31,33,40 Most studies measure the deformability 29,31 or separability 31,41,42 of the magnetic microgels. To the best of our knowledge, the literature misses experimental studies on the interaction strength between MNPs and the microgel network investigated with magnetic experiments.…”