Targeting tumor cells and neovascularization using RGD-functionalized magnetoliposomes.

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ID: 49439
2019
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Abstract
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.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 10 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.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.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.
Reference Key
garcia-ribeiro2019targetinginternational Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Garcia Ribeiro, Rita Sofia;Belderbos, Sarah;Danhier, Pierre;Gallo, Juan;Manshian, Bella B;Gallez, Bernard;Bañobre, Manuel;de Cuyper, Marcel;Soenen, Stefaan J;Gsell, Willy;Himmelreich, Uwe;
Journal international journal of nanomedicine
Year 2019
DOI
10.2147/IJN.S214041
URL
Keywords
MRI tumor targeting fli skov-3 crgd magnetoliposomes

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