The careful selection of zwitterionic nanoparticle coating results in rapid and efficient cell labeling for imaging‐based cell tracking

Abstract The increased clinical application of cell‐based therapies has resulted in a parallel increase in the need for non‐invasive imaging‐based approaches for cell tracking, often through labeling with nanoparticles. An ideal nanoparticle for such applications must be biologically compatible as w...

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Main Authors: Nicholas D. Calvert, Luciana Yu, Olivia C. Sehl, Julia J. Gevaert, Natasha N. Knier, Angelie Rivera‐Rodriguez, Clara S. Goulet, Nitara Fernando, Samantha Flood, Carlos M. Rinaldi‐Ramos, Paula J. Foster, Adam J. Shuhendler
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Language:English
Published: Wiley 2024-12-01
Series:Aggregate
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Online Access:https://doi.org/10.1002/agt2.609
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author Nicholas D. Calvert
Luciana Yu
Olivia C. Sehl
Julia J. Gevaert
Natasha N. Knier
Angelie Rivera‐Rodriguez
Clara S. Goulet
Nitara Fernando
Samantha Flood
Carlos M. Rinaldi‐Ramos
Paula J. Foster
Adam J. Shuhendler
author_facet Nicholas D. Calvert
Luciana Yu
Olivia C. Sehl
Julia J. Gevaert
Natasha N. Knier
Angelie Rivera‐Rodriguez
Clara S. Goulet
Nitara Fernando
Samantha Flood
Carlos M. Rinaldi‐Ramos
Paula J. Foster
Adam J. Shuhendler
author_sort Nicholas D. Calvert
collection DOAJ
description Abstract The increased clinical application of cell‐based therapies has resulted in a parallel increase in the need for non‐invasive imaging‐based approaches for cell tracking, often through labeling with nanoparticles. An ideal nanoparticle for such applications must be biologically compatible as well as readily internalized by cells to ensure adequate and stable cell loading. Surface coatings have been used to make nanoparticle trackers suitable for these purposes, but those currently employed tend to have cytotoxic effects. Zwitterionic ligands are known to be biocompatible and antifouling; however, head‐to‐head evaluation of specific zwitterionic ligands for cell loading has not yet been explored. Magnetic particle imaging (MPI) detects superparamagnetic iron oxide nanoparticles (SPIONs) using time‐varying magnetic fields. Because MPI can produce high‐contrast, real‐time images with no tissue depth limitation, it is an ideal candidate for in vivo cell tracking. In this work, we have conjugated hard (permanently charged) and soft (pKa‐dependently charged) biomimetic zwitterionic ligands to SPIONs and characterized how these ligands changed SPION physicochemical properties. We have evaluated cellular uptake and subcellular localization between zwitterions, how the improvement in cell uptake generated stronger MPI signal for smaller numbers of cells, and how these cells can be tracked in an animal model with greater sensitivity for longer periods of time. Our best‐performing surface coating afforded high cell loading within 4 h, with full signal retention in vivo over 7 days.
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spelling doaj-art-71a5e0d35fb94fecae4472548b319b2c2025-08-20T02:49:08ZengWileyAggregate2692-45602024-12-0156n/an/a10.1002/agt2.609The careful selection of zwitterionic nanoparticle coating results in rapid and efficient cell labeling for imaging‐based cell trackingNicholas D. Calvert0Luciana Yu1Olivia C. Sehl2Julia J. Gevaert3Natasha N. Knier4Angelie Rivera‐Rodriguez5Clara S. Goulet6Nitara Fernando7Samantha Flood8Carlos M. Rinaldi‐Ramos9Paula J. Foster10Adam J. Shuhendler11Department of Chemistry and Biomolecular Sciences University of Ottawa Ottawa Ontario CanadaDepartment of Chemistry and Biomolecular Sciences University of Ottawa Ottawa Ontario CanadaDepartment of Medical Biophysics Western University London Ontario CanadaDepartment of Medical Biophysics Western University London Ontario CanadaDepartment of Medical Biophysics Western University London Ontario CanadaJ. Crayton Pruitt Family Department of Biomedical Engineering University of Florida Gainesville Florida USADepartment of Chemistry and Biomolecular Sciences University of Ottawa Ottawa Ontario CanadaDepartment of Medical Biophysics Western University London Ontario CanadaDepartment of Medical Biophysics Western University London Ontario CanadaJ. Crayton Pruitt Family Department of Biomedical Engineering University of Florida Gainesville Florida USADepartment of Medical Biophysics Western University London Ontario CanadaDepartment of Chemistry and Biomolecular Sciences University of Ottawa Ottawa Ontario CanadaAbstract The increased clinical application of cell‐based therapies has resulted in a parallel increase in the need for non‐invasive imaging‐based approaches for cell tracking, often through labeling with nanoparticles. An ideal nanoparticle for such applications must be biologically compatible as well as readily internalized by cells to ensure adequate and stable cell loading. Surface coatings have been used to make nanoparticle trackers suitable for these purposes, but those currently employed tend to have cytotoxic effects. Zwitterionic ligands are known to be biocompatible and antifouling; however, head‐to‐head evaluation of specific zwitterionic ligands for cell loading has not yet been explored. Magnetic particle imaging (MPI) detects superparamagnetic iron oxide nanoparticles (SPIONs) using time‐varying magnetic fields. Because MPI can produce high‐contrast, real‐time images with no tissue depth limitation, it is an ideal candidate for in vivo cell tracking. In this work, we have conjugated hard (permanently charged) and soft (pKa‐dependently charged) biomimetic zwitterionic ligands to SPIONs and characterized how these ligands changed SPION physicochemical properties. We have evaluated cellular uptake and subcellular localization between zwitterions, how the improvement in cell uptake generated stronger MPI signal for smaller numbers of cells, and how these cells can be tracked in an animal model with greater sensitivity for longer periods of time. Our best‐performing surface coating afforded high cell loading within 4 h, with full signal retention in vivo over 7 days.https://doi.org/10.1002/agt2.609cell trackingmagnetic nanoparticle imaging (MPI)nanoparticle functionalizationnanoparticle uptakesurface chemistryzwitterionic ligands
spellingShingle Nicholas D. Calvert
Luciana Yu
Olivia C. Sehl
Julia J. Gevaert
Natasha N. Knier
Angelie Rivera‐Rodriguez
Clara S. Goulet
Nitara Fernando
Samantha Flood
Carlos M. Rinaldi‐Ramos
Paula J. Foster
Adam J. Shuhendler
The careful selection of zwitterionic nanoparticle coating results in rapid and efficient cell labeling for imaging‐based cell tracking
Aggregate
cell tracking
magnetic nanoparticle imaging (MPI)
nanoparticle functionalization
nanoparticle uptake
surface chemistry
zwitterionic ligands
title The careful selection of zwitterionic nanoparticle coating results in rapid and efficient cell labeling for imaging‐based cell tracking
title_full The careful selection of zwitterionic nanoparticle coating results in rapid and efficient cell labeling for imaging‐based cell tracking
title_fullStr The careful selection of zwitterionic nanoparticle coating results in rapid and efficient cell labeling for imaging‐based cell tracking
title_full_unstemmed The careful selection of zwitterionic nanoparticle coating results in rapid and efficient cell labeling for imaging‐based cell tracking
title_short The careful selection of zwitterionic nanoparticle coating results in rapid and efficient cell labeling for imaging‐based cell tracking
title_sort careful selection of zwitterionic nanoparticle coating results in rapid and efficient cell labeling for imaging based cell tracking
topic cell tracking
magnetic nanoparticle imaging (MPI)
nanoparticle functionalization
nanoparticle uptake
surface chemistry
zwitterionic ligands
url https://doi.org/10.1002/agt2.609
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