Hyaluronic acid-functionalized redox responsive immunomagnetic nanocarrier for circulating tumor cell capture and release

Abstract

Detection of circulating tumor cells (CTCs) in peripheral blood holds significant insights for cancer diagnosis, prognosis evaluation, and precision medicine. To efficiently capture and release CTCs with high viability, we reported the development of hyaluronic acid (HA)-functionalized redox responsive immunomagnetic nanocarrier (Fe3O4@SiO2-SS-HA). First, Fe3O4 nanoparticles were prepared and modified with tetraethyl orthosilicate (TEOS), 3-mercaptopropyltrimethoxysilane (MPTMS) and 2,2 '-dithiodipyridine (DDPy) to form the magnetic substrate (Fe3O4@SiO2-SSPy). Modified with targeted segment HA-functionalized L-cysteine ethyl ester hydrochloride (HA-Cys) via disulfide exchange reaction, the Fe3O4@SiO2-SS-HA was formed. The nanocarrier with prominent magnetic property, targeting ligand, and redox-sensitive disulfide linkages was able to specially capture MCF-7 cells with an efficiency of 92% and effectively release captured cells with an efficiency of 81.4%. Furthermore, the Fe3O4@SiO2-SS-HA could successfully be used for the capture of MCF-7 cells, and the captured cells could be diferntiated from the blood cells. Almost all of released tumor cells kept good viability and a robust proliferative capacity after being re-cultured. It is likely that the as-prepared nanocarrier will serve as a new weapon against CD44 receptor-overexpressed cancer cells.