Publications

Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, N.I.H., Extramural Ppublish 9 citations

PubMed: 37154678 DOI: 10.1021/acs.nanolett.3c01090

Targeted Enzyme Activity Imaging with Quantitative Phase Microscopy.

Nano Lett 23(10):4602-4608

Authors: Swati Tanwar, Lintong Wu, Noah Zahn, Piyush Raj, Behnaz Ghaemi, Arnab Chatterjee, Jeff W M Bulte, Ishan Barman

Affiliations

  • Department of Mechanical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
  • Department of Chemical & Biomolecular Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
  • The Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205, USA.
  • Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
  • Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland 21218, USA.
  • F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Inc. Baltimore, Maryland 21205, USA.
  • Department of Oncology, Johns Hopkins University, Baltimore, Maryland 21287, USA.

Abstract

Quantitative phase imaging (QPI) is a powerful optical imaging modality for label-free, rapid, and three-dimensional (3D) monitoring of cells and tissues. However, molecular imaging of important intracellular biomolecules such as enzymes remains a largely unexplored area for QPI. Herein, we introduce a fundamentally new approach by designing QPI contrast agents that allow sensitive detection of intracellular biomolecules. We report a new class of bio-orthogonal QPI-nanoprobes for high-contrast refractive index (RI) imaging of enzyme activity. The nanoprobes feature silica nanoparticles (SiO NPs) having higher RI than endogenous cellular components and surface-anchored cyanobenzothiazole-cysteine (CBT-Cys) conjugated enzyme-responsive peptide sequences. The nanoprobes specifically aggregated in cells with target enzyme activity, increasing intracellular RI and enabling precise visualization of intracellular enzyme activity. We envision that this general design of QPI-nanoprobes could open doors for spatial-temporal mapping of enzyme activity with direct implications for disease diagnosis and evaluating the therapeutic efficacy.

MeSH

Microscopy, Enzymes, Biotechnology, Cells, Quantitative Phase Imaging

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