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

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) conj...

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Published inPharmaceutics Vol. 13; no. 10; p. 1663
Main Authors Chopra, Meenu, Wu, Jiansha, Yeow, Yen Ling, Winteringham, Louise, Clemons, Tristan D., Saunders, Martin, Kotamraju, Venkata Ramana, Ganss, Ruth, Feindel, Kirk W., Hamzah, Juliana
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 12.10.2021
MDPI
Subjects
Aqueous solutions
Blood vessels
Cancer
Contrast agents
CSG
extracellular matrix
Ligands
Lipids
Magnetic resonance imaging
Metastasis
Morphology
Nanoparticles
Peptides
Tumors
tumour targeting
Ultrasonic imaging
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Summary: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.
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These authors contribute equally to this work.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics13101663