Visual, Label-Free Telomerase Activity Monitor via Enzymatic Etching of Gold Nanorods

Abstract

Early diagnosis and life-long surveillance are clinically important to improve the long-term survival of cancer patients. Telomerase activity is a valuable biomarker for cancer diagnosis, but its measurement often used complex label procedures. Herein, we designed a novel, simple, visual and label-free method for telomerase detection by using enzymatic etching of gold nanorods (GNRs). First, repeating (TTAGGG)x sequences were extented on telomerase substrate (TS) primer. It formed G-quadruplex under the help of Hemin and K+. Second, the obtained horseradish peroxidase mimicking hemin/G-quadruplex catalyzed the H2O2-mediated etching of GNRs to the short GNRs, even to gold nanoparticles (GNPs), generating a series of distinct color changes due to their plasmon-related optical response. Thus, this enzymatic reaction can be easily coupled to telomerase activity, allowing for the detection of telomerase activity based on vivid colors. This can be differentiated sensitively by naked eyes because human eyes are more sensitive to color variations rather than the optical density variations. As a result, telomerase activity can be quantitatively detected ranging from 200 to 15000 HeLa cells mL-1. The detection limit was 90 HeLa cells mL-1 (S/N = 3). Importantly, the application of this method in bladder cancer samples was in agreement with the clinical results. Thus, this method was considerably suitable for point-of-care diagnostics in resource-constrained regions because of the easy readout of results without the use of sophisticated apparatus.