TY - JOUR
T1 - Dextran-Mimetic Quantum Dots for Multimodal Macrophage Imaging In Vivo, Ex Vivo, and In Situ
AU - Deng, Hongping
AU - Konopka, Christian J.
AU - Prabhu, Suma
AU - Sarkar, Suresh
AU - Medina, Natalia Gonzalez
AU - Fayyaz, Muhammad
AU - Arogundade, Opeyemi H.
AU - Vidana Gamage, Hashni Epa
AU - Shahoei, Sayyed Hamed
AU - Nall, Duncan
AU - Youn, Yeoan
AU - Dobrucka, Iwona T.
AU - Audu, Christopher O.
AU - Joshi, Amrita
AU - Melvin, William J.
AU - Gallagher, Katherine A.
AU - Selvin, Paul R.
AU - Nelson, Erik R.
AU - Dobrucki, Lawrence W.
AU - Swanson, Kelly S.
AU - Smith, Andrew M.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (R01 DK112251 to A.M.S. and K.S.S. and R01 CA234025 to E.R.N.), a Department of Defense Breast Cancer Research Program Era of Hope Scholar Award (W81XWH-20-BCRP-EOHS/BC200206 to E.R.N.), a grant from the Cancer Center at Illinois and the Grainger College of Engineering, and funds from the University of Illinois at Urbana-Champaign. This work was carried out in part in the Molecular Imaging Laboratory of the Biomedical Imaging Center at the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign.
Publisher Copyright:
© 2022 American Chemical Society
PY - 2022/2/22
Y1 - 2022/2/22
N2 - Macrophages are white blood cells with diverse functions contributing to a healthy immune response as well as the pathogenesis of cancer, osteoarthritis, atherosclerosis, and obesity. Due to their pleiotropic and dynamic nature, tools for imaging and tracking these cells at scales spanning the whole body down to microns could help to understand their role in disease states. Here we report fluorescent and radioisotopic quantum dots (QDs) for multimodal imaging of macrophage cells in vivo, ex vivo, and in situ. Macrophage specificity is imparted by click-conjugation to dextran, a biocompatible polysaccharide that natively targets these cell types. The emission spectral band of the crystalline semiconductor core was tuned to the near-infrared for optical imaging deep in tissue, and probes were covalently conjugated to radioactive iodine for nuclear imaging. The performance of these probes was compared with all-organic dextran probe analogues in terms of their capacity to target macrophages in visceral adipose tissue using in vivo positron emission tomography/computed tomography (PET/CT) imaging, in vivo fluorescence imaging, ex vivo fluorescence, post-mortem isotopic analyses, and optical microscopy. All probe classes exhibited equivalent physicochemical characteristics in aqueous solution and similar in vivo targeting specificity. However, dextran-mimetic QDs provided enhanced signal-to-noise ratio for improved optical quantification, long-term photostability, and resistance to chemical fixation. In addition, the vascular circulation time for the QD-based probes was extended 9-fold compared with dextran, likely due to differences in conformational flexibility. The enhanced photophysical and photochemical properties of dextran-mimetic QDs may accelerate applications in macrophage targeting, tracking, and imaging across broad resolution scales, particularly advancing capabilities in single-cell and single-molecule imaging and quantification.
AB - Macrophages are white blood cells with diverse functions contributing to a healthy immune response as well as the pathogenesis of cancer, osteoarthritis, atherosclerosis, and obesity. Due to their pleiotropic and dynamic nature, tools for imaging and tracking these cells at scales spanning the whole body down to microns could help to understand their role in disease states. Here we report fluorescent and radioisotopic quantum dots (QDs) for multimodal imaging of macrophage cells in vivo, ex vivo, and in situ. Macrophage specificity is imparted by click-conjugation to dextran, a biocompatible polysaccharide that natively targets these cell types. The emission spectral band of the crystalline semiconductor core was tuned to the near-infrared for optical imaging deep in tissue, and probes were covalently conjugated to radioactive iodine for nuclear imaging. The performance of these probes was compared with all-organic dextran probe analogues in terms of their capacity to target macrophages in visceral adipose tissue using in vivo positron emission tomography/computed tomography (PET/CT) imaging, in vivo fluorescence imaging, ex vivo fluorescence, post-mortem isotopic analyses, and optical microscopy. All probe classes exhibited equivalent physicochemical characteristics in aqueous solution and similar in vivo targeting specificity. However, dextran-mimetic QDs provided enhanced signal-to-noise ratio for improved optical quantification, long-term photostability, and resistance to chemical fixation. In addition, the vascular circulation time for the QD-based probes was extended 9-fold compared with dextran, likely due to differences in conformational flexibility. The enhanced photophysical and photochemical properties of dextran-mimetic QDs may accelerate applications in macrophage targeting, tracking, and imaging across broad resolution scales, particularly advancing capabilities in single-cell and single-molecule imaging and quantification.
KW - PET
KW - infrared
KW - molecular imaging
KW - optical
KW - phagocyte
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U2 - 10.1021/acsnano.1c07010
DO - 10.1021/acsnano.1c07010
M3 - Article
C2 - 35107994
AN - SCOPUS:85124298963
SN - 1936-0851
VL - 16
SP - 1999
EP - 2012
JO - ACS Nano
JF - ACS Nano
IS - 2
ER -