Sensitive detection of folate receptor-positive circulating tumor cells based on intracellular uptake of the PbS nanoparticle cluster-loaded phospholipid micelles decorated with folic acid in combination with E-DNA sensor

Abstract

Developing methods for the circulating tumor cells (CTCs) detection is important for noninvasive cancer diagnosis. A sensitive method for homogeneous electrochemical detection of CTCs was developed based on the affinity of folic acid (FA) for folate receptor (FR), which is overexpressed on the CTC surface. The PbS nanoparticle cluster-loaded phospholipid micelles decorated with FA were prepared and used as a nanoprobe. The specific binding of FA to FR-positive CTCs leads to the uptake of the nanoprobes into the CTCs. Cellular imaging assay showed the excellent biocompatibility and selectivity of nanoprobes. After separation of intracellular nanoprobes and the residual free nanoprobes in the solution by centrifugation, nanoprobes in the cell were dissolved using acid. The amount of the target cells was quantified by the electrochemical detection of Pd2+ using the electrochemical DNA (E-DNA) sensor, which was fabricated based on the self-assembly of probe DNA on the flowerlike gold nanostructures modified the screen-printed carbon electrode (SPCE). Because of the large quantities of detectable Pd2+ contained in the nanoprobes, the signal amplification effect was achieved. The developed electrochemical assay allows the detection of ∼5 cells from 1 mL of sample. Studies with both healthy individuals and cancer patient blood samples demonstrate that the assay is sensitive and FR-positive CTCs specific.