Targeting tumor cells and neovascularization using RGD-functionalized magnetoliposomes
Received 2 May 2019
Accepted for publication 29 June 2019
Published 29 July 2019 Volume 2019:14 Pages 5911—5924
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Thomas J. Webster
Rita Sofia Garcia Ribeiro,1,* Sarah Belderbos,1,* Pierre Danhier,2 Juan Gallo,2 Bella B Manshian,1 Bernard Gallez,2 Manuel Bañobre,3 Marcel de Cuyper,4 Stefaan J Soenen,1 Willy Gsell,1 Uwe Himmelreich1
1Biomedical MRI/MoSAIC, Department of Imaging and Pathology, Biomedical Sciences Group, Leuven B-3000, Belgium; 2Biomedical Magnetic Resonance Research Group, Louvain Drug Research Institute, Université Catholique De Louvain, Brussels B-1200, Belgium; 3Diagnostic Tools and Methods/Advanced (Magnetic) Theranostic Nanostructures Lab, International Iberian Nanotechnology Laboratory (INL), PT-Braga 4715-330, Portugal; 4Laboratory of Bionanocolloids, Interdisciplinary Research Centre, KULAK/KU Leuven, Kortrijk B-8500, Belgium
*These authors contributed equally to this work
Purpose: Magnetoliposomes (MLs) have shown great potential as magnetic resonance imaging contrast agents and as delivery vehicles for cancer therapy. Targeting the MLs towards the tumor cells or neovascularization could ensure delivery of drugs at the tumor site. In this study, we evaluated the potential of MLs targeting the αvβ3 integrin overexpressed on tumor neovascularization and different tumor cell types, including glioma and ovarian cancer.
Methods: MLs functionalized with a Texas Red fluorophore (anionic MLs), and with the fluorophore and the cyclic Arginine-Glycine-Aspartate (cRGD; cRGD-MLs) targeting the αvβ3 integrin, were produced in-house. Swiss nude mice were subcutaneously injected with 107 human ovarian cancer SKOV-3 cells. Tumors were allowed to grow for 3 weeks before injection of anionic or cRGD-MLs. Biodistribution of MLs was followed up with a 7T preclinical magnetic resonance imaging (MRI) scanner and fluorescence imaging (FLI) right after injection, 2h, 4h, 24h and 48h post injection. Ex vivo intratumoral ML uptake was confirmed using FLI, electron paramagnetic resonance spectroscopy (EPR) and histology at different time points post injection.
Results: In vivo, we visualized a higher uptake of cRGD-MLs in SKOV-3 xenografts compared to control, anionic MLs with both MRI and FLI. Highest ML uptake was seen after 4h using MRI, but only after 24h using FLI indicating the lower sensitivity of this technique. Furthermore, ex vivo EPR and FLI confirmed the highest tumoral ML uptake at 4 h. Last, a Perl’s stain supported the presence of our iron-based particles in SKOV-3 xenografts.
Conclusion: Uptake of cRGD-MLs can be visualized using both MRI and FLI, even though the latter was less sensitive due to lower depth penetration. Furthermore, our results indicate that cRGD-MLs can be used to target SKOV-3 xenograft in Swiss nude mice. Therefore, the further development of this particles into theranostics would be of interest.
Keywords: tumor targeting, SKOV-3, cRGD, magnetoliposomes, MRI, FLI