Modulation of Gold Nanorod Growth via the Proteolysis of Dithiol Peptides for Enzymatic Biomarker Detection

• Published in: ACS applied materials & interfaces Vol. 13; no. 38; pp. 45236 - 45243
• Main Authors: Creyer, Matthew N, Jin, Zhicheng, Moore, Colman, Yim, Wonjun, Zhou, Jiajing, Jokerst, Jesse V
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 29-09-2021
• Subjects: Animals; Aprotinin - chemistry; Aprotinin - urine; Biological and Medical Applications of Materials and Interfaces; Biomarkers - analysis; Biomarkers - chemistry; Cattle; Colorimetry; Enzyme Assays - methods; Gold - chemistry; Humans; Limit of Detection; Nanotubes - chemistry; Peptides - chemistry; Proof of Concept Study; Proteolysis; Swine; Trypsin - analysis; Trypsin - chemistry; Trypsin Inhibitors - chemistry; Trypsin Inhibitors - urine; biosensing; peptides; gold nanorods; enzyme activity; biomarkers; proteolysis
• ISSN: 1944-8244; 1944-8252
• DOI: 10.1021/acsami.1c11620

Gold nanorods possess optical properties that are tunable and highly sensitive to variations in their aspect ratio (length/width). Therefore, the development of a sensing platform where the gold nanorod morphology (i.e., aspect ratio) is modulated in response to an analyte holds promise in achieving ultralow detection limits. Here, we use a dithiol peptide as an enzyme substrate during nanorod growth. The sensing mechanism is enabled by the substrate design, where the dithiol peptide contains an enzyme cleavage site in-between cysteine amino acids. When cleaved, the peptide dramatically impacts gold nanorod growth and the resulting optical properties. We demonstrate that the optical response can be correlated with enzyme concentration and achieve a 45 pM limit of detection. Furthermore, we extend this sensing platform to colorimetrically detect tumor-associated inhibitors in a biologically relevant medium. Overall, these results present a subnanomolar method to detect proteases that are critical biomarkers found in cancers, infectious diseases, and inflammatory disorders.