Enhanced Detection of Desmoplasia By Targeted Delivery of Iron Oxide Nanoparticles To the Tumour-Specific Extracellular Matrix

Authors

Meenu Chopra, The University of Western Australia
Jiansha Wu, The University of Western Australia
Yen Ling Yeow, The University of Western Australia
Louise Winteringham, The University of Western Australia
Tristan D. Clemons, The University of Western AustraliaFollow
Martin Saunders, The University of Western Australia
Venkata Ramana Kotamraju, Sanford Burnham Prebys Medical Discovery Institute
Ruth Ganss, The University of Western Australia
Kirk W. Feindel, The University of Western Australia
Juliana Hamzah, The University of Western Australia

Document Type

Article

Publication Date

10-1-2021

School

Polymer Science and Engineering

Abstract

Diagnostic imaging of aggressive cancer with a high stroma content may benefit from the use of imaging contrast agents targeted with peptides that have high binding affinity to the extracellular matrix (ECM). In this study, we report the use of superparamagnetic iron-oxide nanoparticles (IO-NP) conjugated to a nonapeptide, CSGRRSSKC (CSG), which specifically binds to the laminin-nidogen-1 complex in tumours. We show that CSG-IO-NP accumulate in tumours, predominantly in the tumour ECM, following intravenous injection into a murine model of pancreatic neuroendocrine tumour (PNET). In contrast, a control untargeted IO-NP consistently show poor tumour uptake, and IO-NP conjugated to a pentapeptide. CREKA that bind fibrin clots in blood vessels show restricted uptake in the angiogenic vessels of the tumours. CSG-IO-NP show three-fold higher intratumoral accumulation compared to CREKA-IO-NP. Magnetic resonance imaging (MRI) T₂-weighted scans and T₂ relaxation times indicate significant uptake of CSG-IO-NP irrespective of tumour size, whereas the uptake of CREKA-IO-NP is only consistent in small tumours of less than 3 mm in diameter. Larger tumours with significantly reduced tumour blood vessels show a lack of CREKA-IO-NP uptake. Our data suggest CSG-IO-NP are particularly useful for detecting stroma in early and advanced solid tumours.

Comments

© Pharmaceutics

Publication Title

Pharmaceutics

Volume

13

Issue

10

Recommended Citation

Chopra, M., Wu, J., Yeow, Y., Winteringham, L., Clemons, T., Saunders, M., Kotamraju, V., Ganss, R., Feindel, K., Hamzah, J. (2021). Enhanced Detection of Desmoplasia By Targeted Delivery of Iron Oxide Nanoparticles To the Tumour-Specific Extracellular Matrix. Pharmaceutics, 13(10).
Available at: https://aquila.usm.edu/fac_pubs/19454