NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Strategic grant

Targeted, radiolabelled near-infrared quantum dots for high sensitivity and resolution, dual modality imaging of human tumours in mice

A pink eppendorf rack

At a glance

Completed
Award date
November 2014 - October 2017
Grant amount
£369,898 (Co-funded by EPSRC)
Principal investigator
Dr Anna Grabowska

Co-investigator(s)

Institute
University of Nottingham

R

  • Reduction

Contents

Overview

Aims

The aim of this project is to reduce the number of mice used in preclinical anti-cancer drug development by developing and applying novel near infrared quantum dots (NIR-QDs) to improve the sensitivity and resolution of preclinical imaging. This will increase the amount of information generated in each animal, reducing the overall number of animals required per study.

Background

Current models used for testing anti-cancer drugs are often not very representative of real patient tumours and so may not correctly identify drugs likely to work well in the clinic. Imaging the growth of cancer cells in animal models, and monitoring the way that the different cells within the tumours behave and interact with each other, which are important in determining drug response, is difficult with current methods. This project will develop novel NIR-QDs which fluoresce at a higher wavelength than currently available standard fluorescent probes. This will provide a more sensitive imaging approach, allowing signals to be detected at deeper sites within the body and improving the quality of the images obtained.

The application of these new probes will allow (i) more detailed information to be gained from each animal used, (ii) repeat imaging of the same animal over time, and (ii) the use of advanced models which provide more relevant information about how useful a drug is likely to be in the clinic.

Research details and methods

The NIR-QDs developed during the course of this project will be designed so that they do not photo-bleach, will be water-soluble, and optically active in the NIR wavelength, providing improved tissue penetration and sensitivity. They will incorporate targeting ligands for uptake by specific populations of cells within the tumour which will allow the growth and drug response of cancer cells or supporting cells within the tumours to be followed. They will also include a positron-emitting radionuclide label which will allow them to be used for positron emission tomography (PET) imaging as well as fluorescence imaging, which will provide a further improvement in the resolution of the images that can be obtained, and will facilitate dual imaging in the same animal.

Impacts

Publications

l-Ani AW et al. (2019). Listeria innocua Dps as a nanoplatform for bioluminescence based photodynamic therapy utilizing Gaussia princeps luciferase and zinc protoporphyrin IX. Nanomedicine 20:102005. doi: 10.1016/j.nano.2019.04.008

Liu Z et al. (2019). Synthesis of folic acid functionalized gold nanoclusters for targeting folate receptorpositive cells. Nanotechnology 30(50):5102. doi: 10.1088/1361-6528/ab437c

Tchoryk A et al. (2019). Penetration and Uptake of Nanoparticles in 3D Tumor Spheroids. Bioconjugate chemistry 30(5):1371–1384. doi: 10.1021/acs.bioconjchem.9b00136

Zhang Q et al. (2019). Numerical Simulation of a Scanning Illumination System for Deep Tissue Fluorescence Imaging. Journal of Imaging 5(11):83. doi: 10.3390/jimaging5110083

Zamberlan F et al. (2018). Stable DHLA-PEG capped PbS quantum dots: from synthesis to near-infrared biomedical imaging. Journal of Materials Chemistry B 6:550-555. doi: 10.1039/C7TB02912H

Austin M et al. (2017). Breast cancer induced nociceptor aberrant growth and collateral sensory axonal branching. Oncotarget 8(4):76606-76621. doi: 10.18632/oncotarget.20609

Turyanska L et al. (2016). Developing Mn-doped lead sulfide quantum dots for MRI labels. Journal of Materials Chemistry B 4:6797-6802. doi: 10.1039/C6TB02574A

Kuruppu AI et al. (2015). An apoferritin-based drug delivery system for the tyrosine kinase inhibitor Gefitinib. Adv Healthc Mater. 4(18):2816-21. doi: 10.1002/adhm.201500389

Zamberlan F et al. (2015). Molecular Sensing with Hyperpolarized (129) Xe Using Switchable Chemical Exchange Relaxation Transfer. Chemphyschem 16(11):2294-8. doi: 10.1002/cphc.201500367