Detection of folic acid and imaging of folate receptor overexpressed cancer cells via a far-red silver nanoclusters with Baseline Resolved Between Excitation and Emission

Abstract

In this work, we designed and synthesized a novel chemically stable fluorescent sensor of far-red emitting silver nanoclusters (PEI-AgNCs) by chemical reduction synthesis and ultrasonic resonance, in which polyethylenimine (PEI) was used as the synthetic template and 2-mercaptobenzothiazole (MBT) and sodium citrate (SC) were used as reducing agents. Due to the high electronegativity of benzothiazole, the antioxidant capacity of PEI-AgNCs was ensured. The PEI-AgNCs were found to be spherical with an average diameter of 2.1 nm, as observed by transmission electron microscopy (TEM). In addition, with a laser excitation of 348 nm, PEI-AgNCs showed the maximum emission intensity at 631 nm with a Stokes shift of 283 nm. Therefore, the use of the nanomaterial for bioimaging not only prevented the interference of biological background fluorescence, but also eliminated the crosstalk between excitation and emission light and the influence of light scattering on experimental results. Fluorescence titration experiment revealed that the fluorescence emission of PEI-AgNCs prepared in this work could be quenched by folic acid (FA) through electron transfer, and the FA in the range of 0.06–1.7 μM and 1.7–20 μM showed an excellent linear response with a detection limit of 12 nM (Sb/K = 3). Moreover, the test probe was successfully applied to the detection of FA in real samples with an average recovery of 98.6–102.3%. Finally, based on different expression levels of folate receptors (FRs) on the surface of different cells, HeLa cells were used as a model to evaluate the feasibility of FRs as fluorescent turn-on nanoprobes for tumor cell-targeted imaging. The results showed that the fluorescence intensity of HeLa cells was consistent with their FRs expression levels, demonstrating their potentiality for tumor cell-targeted imaging.