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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/10/1663 |
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| author | Meenu Chopra Jiansha Wu Yen Ling Yeow Louise Winteringham Tristan D. Clemons Martin Saunders Venkata Ramana Kotamraju Ruth Ganss Kirk W. Feindel Juliana Hamzah |
| author_facet | Meenu Chopra Jiansha Wu Yen Ling Yeow Louise Winteringham Tristan D. Clemons Martin Saunders Venkata Ramana Kotamraju Ruth Ganss Kirk W. Feindel Juliana Hamzah |
| author_sort | Meenu Chopra |
| collection | DOAJ |
| description | 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) T<sub>2</sub>-weighted scans and T<sub>2</sub> 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. |
| first_indexed | 2024-03-10T06:16:43Z |
| format | Article |
| id | doaj.art-db1cfddc342e4743b02e366ad0f91e33 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T06:16:43Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-db1cfddc342e4743b02e366ad0f91e332023-11-22T19:39:22ZengMDPI AGPharmaceutics1999-49232021-10-011310166310.3390/pharmaceutics13101663Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular MatrixMeenu Chopra0Jiansha Wu1Yen Ling Yeow2Louise Winteringham3Tristan D. Clemons4Martin Saunders5Venkata Ramana Kotamraju6Ruth Ganss7Kirk W. Feindel8Juliana Hamzah9Harry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands 6009, AustraliaHarry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands 6009, AustraliaHarry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands 6009, AustraliaHarry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands 6009, AustraliaSchool of Molecular Sciences, The University of Western Australia, Crawley 6009, AustraliaCentre for Microscopy, Characterisation and Analysis, The University of Western Australia, Nedlands 6009, AustraliaCancer Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USAHarry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands 6009, AustraliaCentre for Microscopy, Characterisation and Analysis, The University of Western Australia, Nedlands 6009, AustraliaHarry Perkins Institute of Medical Research, Centre for Medical Research, QEII Medical Centre, The University of Western Australia, Nedlands 6009, AustraliaDiagnostic 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) T<sub>2</sub>-weighted scans and T<sub>2</sub> 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.https://www.mdpi.com/1999-4923/13/10/1663tumour targetingextracellular matrixCSGnanoparticlesmagnetic resonance imaging |
| spellingShingle | Meenu Chopra Jiansha Wu Yen Ling Yeow Louise Winteringham Tristan D. Clemons Martin Saunders Venkata Ramana Kotamraju Ruth Ganss Kirk W. Feindel Juliana Hamzah Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix Pharmaceutics tumour targeting extracellular matrix CSG nanoparticles magnetic resonance imaging |
| title | Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix |
| title_full | Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix |
| title_fullStr | Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix |
| title_full_unstemmed | Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix |
| title_short | Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix |
| title_sort | enhanced detection of desmoplasia by targeted delivery of iron oxide nanoparticles to the tumour specific extracellular matrix |
| topic | tumour targeting extracellular matrix CSG nanoparticles magnetic resonance imaging |
| url | https://www.mdpi.com/1999-4923/13/10/1663 |
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