4.8 Article

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

Journal

ACS APPLIED MATERIALS & INTERFACES
Volume 13, Issue 38, Pages 45236-45243

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c11620

Keywords

proteolysis; enzyme activity; peptides; biosensing; gold nanorods; biomarkers

Funding

  1. NIH [R01 DE031114, T32 CA153915]
  2. ARCS (Achievement Reward for College Scientists)
  3. National Science Foundation [DGE-1650112]

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Gold nanorods with tunable optical properties can be used to detect enzyme concentrations and specific inhibitors with low detection limits, making them suitable for detecting diseases such as cancer. The sensing mechanism involves using a dithiol peptide as an enzyme substrate during nanorod growth, with the optical response correlated to enzyme concentration.
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.

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