Direct ultrasensitive electrochemical detection of breast cancer biomarker-miRNA-21 employing an aptasensor based on a microgel nanoparticle composite

Breast cancer is a common disease with high morbidity and mortality among women worldwide. Serum miRNA-21 expression is higher in breast cancer patients and can be employed as a predictor for early breast cancer diagnosis. There is an urgent need for a sensitive, convenient and cost-effective biosensor to assist in the direct diagnosis of breast cancer through clinical biomarkers. In this article, a highly sensitive microgel nanocomposite-based electrochemical aptasensor is prepared for the detection of miRNA-21. The microgel particles of gold nanoparticles are wrapped in a mixture of acrylic acid (AAc) and N-isopropylacrylamide (NIPAm) polymerization. This leads to a porous network structure which can provide a highly biocompatible and anti-fouling microenvironment, similar to that of aqueous biological tissue for RNA capture reaction. Complementary to miRNA-21, an amino-modified oligonucleotide chain capture probe is covalently immobilized on the microgel material, while the hybridization of miRNA-21 with the capture probe is monitored by different pulse voltammetry (DPV). The sensing platform can directly and accurately detect target miRNAs in serum without sample preparation and purification. The concentration response of the aptasensor presents a linear range of 10 aM to 1 pM as well as a detection limit of 1.35 aM. The aptasensor also exhibits noticeable selectivity, stability and reproducibility. Simultaneously, we successfully apply this method to the subsequent detection of serum miRNA-21 in 2 breast cancer patients before treatment and after recovery respectively. The consequence proves that the method has promising potential applications in the early diagnosis and treatment of breast cancer patients.