An super sensitive Multi-Modal controlled release biosensor with label- and enzyme- free assisted single step simultaneously detect multiple breast cancer biomarkers

Abstract

Despite the fact that homogeneous biosensing strategies have been proven to be advantageous, it remains a difficult task to identify multiple tumor biomarkers. Our proposition entails the creation of a groundbreaking biosensor that combines electrochemical and fluorescent techniques, enabling simultaneous detect multiple biomarkers with label- and enzyme-free assistance in a single step. Porous UIO-66-NH2 nanovessels loaded with 3,3′,5,5′ −tetramethylbenzidine (TMB) and methylene blue (MB) double signal dyes, along with double-stranded DNA (dsDNA) formed by the aptamer chain of human epidermal growth factor receptor-2 (HER2) and estrogen receptor (ER) and its complementary chain as a gated switch to the envelope MOFs, were utilized to create functional MOFs (dsDNA@MB@UIO and dsDNA@TMB@UIO). When HER2 and ER targets are present, the chain replacement reaction led to the formation of a biomarker-aptamer complex, resulting in the destruction of the dsDNA structure on the surface of MOF and the liberation of MB and TMB. The concentration of the two target biomarkers determines the strength of the electrochemical and fluorescent signals produced. By combining targeted biomarkers, signal enhancement, and dual-signal detection into one unified process, the amount of test error caused by the multi-step detection needed in prior studies is significantly decreased. We executed the detect HER2 and ER, achieving detection limits of 4.7 and 5.9 fg/mL in 4.7–1000 pg/mL linear range with good selectivity, stability, reproducibility, and acceptable applicability. The proposed biosensor for developing dsDNA@MB@UIO and dsDNA@TMB@UIO is promising for the early and sensitive detection of cancer biomarkers.