Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix

Meenu Chopra; Jiansha Wu; Yen Ling Yeow; Louise Winteringham; Tristan D Clemons; Martin Saunders; Venkata Ramana Kotamraju; Ruth Ganss; Kirk W Feindel; Juliana Hamzah

doi:10.3390/pharmaceutics13101663

Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix

Pharmaceutics. 2021 Oct 12;13(10):1663. doi: 10.3390/pharmaceutics13101663.

Authors

Affiliations

¹ Harry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands 6009, Australia.
² School of Molecular Sciences, The University of Western Australia, Crawley 6009, Australia.
³ School of Polymer Science and Engineering, University of Southern Mississippi, Hattiesburg, MS 39406, USA.
⁴ Centre for Microscopy, Characterisation and Analysis, The University of Western Australia, Nedlands 6009, Australia.
⁵ Cancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
⁶ Curtin Health Innovation Research Institute, Curtin University, Perth 6102, Australia.

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.

Keywords: CSG; extracellular matrix; magnetic resonance imaging; nanoparticles; tumour targeting.

Abstract

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