As
a biomarker of hepatocellular carcinoma (HCC) biopsy, circulating
tumor cells (CTCs) are often used in the diagnosis of cancer and treatment
guidance. For CTCs detection, immuno-magnetic nanoparticles (IMNs)
are one of the most commonly used platforms. However, the nonspecific
adsorption of proteins and non-tumor cells weakens the performance
of IMNs to capture CTCs. In this work, we developed an IMNs platform
which was constructed by a biomimetic protein corona precoating and
a polyethylene glycol (PEG) spacer to form the PEG and corona-coated
IMNs (IP-CMNs). Due to the dual stealth effect of protein corona precoating
and PEG spacer, the nonspecific protein adsorption and cell binding
of P-CMNs could reduce by ∼5.5- and ∼5.4-fold, respectively,
compared with those of unmodified particles. Furthermore, the PEG
spacer could not only reduce the interaction between IP-CMNs and leukocytes
but also enhance the capture performance toward tumor cells. By using
artificial blood samples, the capture efficiency of IP-CMNs toward
rare CTCs was found to be 88.3%, while it was 70.5% by using commercial
IMNs. Finally, CTCs were successfully isolated in all HCC patient
blood samples (7/7) using IP-CMNs. These results provide insight into
the use of the multifunctional nanoplatform as a useful tool for CTCs
detection.