Multilocus-dendritic folic acid functionalized magnetic nanoparticles enable efficient capture and gentle release of...

Circulating tumor cells (CTCs) are critical biomarkers for early cancer diagnosis, disease progression monitoring, and personalized therapy. However, the high-efficiency capture, gentle release, and preservation of viable CTCs remain significant challenges due to their low abundance and fragile nature. In this study, a novel platform based on multilocus-dendritic folic acid (FA) functionalized magnetic nanoparticles (Fe₃O₄@PEI@SPDP@FA) was designed for high-efficiency capture and gentle release of model CTCs (Hela and MDA-MB-231 cells). Polyethyleneimine (PEI) was employed to expand the surface area available for conjugation, based on this foundation, succinimidyl 3-[2-pyridyldithio] propionate (SPDP) containing reversible disulfide bonds was incorporated to facilitate the gentle release of model CTCs, thereby endowing the materials with dynamic responsive properties. Then the lipidomics analysis of released cells was studied to explore the impact of capture and release on cell metabolism. The system leverages the high specificity and strong affinity between folic acid (FA) and folate receptors (FRs), which are overexpressed on the surface of certain CTCs. Under an applied magnetic attraction, model CTCs were efficiently captured with a success rate exceeding 80 %. Importantly, the captured model CTCs were gently released using dithiothreitol (DTT) treatment, achieving a release efficiency of over 70 % while maintaining high cell viability (>95 %). The results of lipidomics analysis for released cells showed that two sets of samples had no significant difference. By integrating rapid magnetic isolation, high-efficiency capture, and gentle release into a single system, this platform enables to develop viable downstream analysis of model CTCs, which is expected to provide new insights for early cancer monitoring.