Multimodal cell tracking from systemic administration to tumour growth by combining gold nanorods and reporter genes

Author:

Comenge Joan1,Sharkey Jack23,Fragueiro Oihane4,Wilm Bettina23ORCID,Brust Mathias4ORCID,Murray Patricia23ORCID,Levy Raphael1ORCID,Plagge Antonius23ORCID

Affiliation:

1. Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom

2. Department of Cellular and Molecular Physiology, University of Liverpool, Liverpool, United Kingdom

3. Centre for Preclinical Imaging, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom

4. Department of Chemistry, University of Liverpool, Liverpool, United Kingdom

Abstract

Understanding the fate of exogenous cells after implantation is important for clinical applications. Preclinical studies allow imaging of cell location and survival. Labelling with nanoparticles enables high sensitivity detection, but cell division and cell death cause signal dilution and false positives. By contrast, genetic reporter signals are amplified by cell division. Here, we characterise lentivirus-based bi-cistronic reporter gene vectors and silica-coated gold nanorods (GNRs) as synergistic tools for cell labelling and tracking. Co-expression of the bioluminescence reporter luciferase and the optoacoustic reporter near-infrared fluorescent protein iRFP720 enabled cell tracking over time in mice. Multispectral optoacoustic tomography (MSOT) showed immediate biodistribution of GNR-labelled cells after intracardiac injection and successive clearance of GNRs (day 1–15) with high resolution, while optoacoustic iRFP720 detection indicated tumour growth (day 10–40). This multimodal cell tracking approach could be applied widely for cancer and regenerative medicine research to monitor short- and long-term biodistribution, tumour formation and metastasis.

Funder

Medical Research Council

Seventh Framework Programme

UK Regenerative Medicine Platform

H2020 Marie Skłodowska-Curie Actions

Biotechnology and Biological Sciences Research Council

Engineering and Physical Sciences Research Council

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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