Your browser doesn't support javascript.
Activatable Carbocyanine Dimers for Photoacoustic and Fluorescent Detection of Protease Activity.
Moore, Colman; Borum, Raina M; Mantri, Yash; Xu, Ming; Fajtová, Pavla; O'Donoghue, Anthony J; Jokerst, Jesse V.
  • Moore C; Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, United States.
  • Borum RM; Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, United States.
  • Mantri Y; Department of Bioengineering, University of California, San Diego, La Jolla, California 92093, United States.
  • Xu M; Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, United States.
  • Fajtová P; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, United States.
  • O'Donoghue AJ; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093, United States.
  • Jokerst JV; Department of Nanoengineering, University of California, San Diego, La Jolla, California 92093, United States.
ACS Sens ; 6(6): 2356-2365, 2021 06 25.
Article in English | MEDLINE | ID: covidwho-1243274
ABSTRACT
Activatable contrast agents are of ongoing research interest because they offer low background and high specificity to the imaging target. Engineered sensitivity to protease activity is particularly desirable because proteases are critical biomarkers in cancer, infectious disease, inflammatory disorders, and so forth. Herein, we developed and characterized a set of peptide-linked cyanine conjugates for dual-modal detection of protease activity via photoacoustic (PA) and fluorescence imaging. The peptide-dye conjugates were designed to undergo contact quenching via intramolecular dimerization and contained n dyes (n = 2, 3, or 4) with n - 1 cleavable peptide substrates. The absorption peaks of the conjugates were blue-shifted 50 nm relative to the free dye and had quenched fluorescence. This effect was sensitive to solvent polarity and could be reversed by solvent switching from water to dimethyl sulfoxide. Employing trypsin as a model protease, we observed a 2.5-fold recovery of the peak absorbance, 330-4600-fold fluorescent enhancement, and picomolar detection limits following proteolysis. The dimer probe was further characterized for PA activation. Proteolysis released single dye-peptide fragments that produced a 5-fold PA enhancement through the increased absorption at 680 nm with nanomolar sensitivity to trypsin. The peptide substrate could also be tuned for protease selectivity; as a proof-of-concept, we detected the main protease (Mpro) associated with the viral replication in SARS-CoV-2 infection. Last, the activated probe was imaged subcutaneously in mice and signal was linearly correlated to the cleaved probe. Overall, these results demonstrate a tunable scaffold for the PA molecular imaging of protease activity with potential value in areas such as disease monitoring, tumor imaging, intraoperative imaging, in vitro diagnostics, and point-of-care sensing.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Photoacoustic Techniques / COVID-19 Type of study: Diagnostic study Limits: Animals / Humans Language: English Journal: ACS Sens Year: 2021 Document Type: Article Affiliation country: Acssensors.1c00518

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Photoacoustic Techniques / COVID-19 Type of study: Diagnostic study Limits: Animals / Humans Language: English Journal: ACS Sens Year: 2021 Document Type: Article Affiliation country: Acssensors.1c00518