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Capture and separation of circulating tumor cells using functionalized magnetic nanocomposites with simultaneous in situ chemotherapy

Chunmiao Liu,Baochan Yang,Xue Chen,Zunfu Hu,Zhichao Dai,Dongjiang Yang,Xiuwen Zheng,Xilin She,Qingyun Liu

Circulating tumor cells (CTCs) are a type of rare cell that are firstly shed from solid tumors and then exist in the bloodstream. The effective capture and separation of CTCs has significant meaning in cancer diagnosis and prognosis. In this study, novel Fe3O4–FePt magnetic nanocomposites (Fe3O4–FePt MNCs) were constructed by integrating face centered cubic (fcc) FePt nanoparticles (NPs) onto the surface of the Fe3O4@SiO2 core. After further modification with NH2–PEG–COOH and the tumor-targeting molecule tLyP-1, the acquired Fe3O4–FePt MNCs possesses excellent biocompatibility and stability and could efficiently target and capture tLyP-1 receptor-positive CTCs. Based on the acidic microenvironment within cancer cells, the FePt layer could rapidly release active Fe2+ ions, which could catalyze H2O2 into reactive oxygen species (ROS) and further induce in situ apoptosis in cancer cells while having no distinct cytotoxicity to normal cells. Moreover, the Fe3O4@SiO2 core with its intrinsic magnetism has huge potential for the bioseparation of CTCs. The in vitro ROS fluorescence imaging experiments and cell capture and separation experiments indicated that the Fe3O4–FePt MNCs could specifically capture and separate cancer cells in the CTCs model and further induce in situ apoptosis. Therefore, the Fe3O4–FePt MNCs could serve as a promising multifunctional nanoseparator for efficiently capturing CTCs and simultaneously inducing in situ chemotherapy.