Polyethylenimine-coated superparamagnetic iron oxide nanoparticles impair in vitro and in vivo angiogenesis

• Published in: Nanomedicine Vol. 21; p. 102063
• Main Authors: Mulens-Arias, Vladimir, Rojas, José Manuel, Sanz-Ortega, Laura, Portilla, Yadileiny, Pérez-Yagüe, Sonia, Barber, Domingo F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2019
• Subjects: Endothelial cells; Macrophage; Magnetic targeting; PEI-coated SPION; Tube formation; Tumor angiogenesis; Magnetic targeting; PEI-coated SPION; Tumor angiogenesis; Tube formation; Endothelial cells; Macrophage
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2019.102063

Endothelial cells are essential to tumor vascularization and impairing their activity can potentially limit tumor growth. Since polyethylenimine (PEI)-coated superparamagnetic iron oxide nanoparticles (SPIONs) are bioactive nanosystems that modulate inflammatory macrophage responses and limit tumor cell invasion, we evaluated their effects on endothelial cell angiogenesis. PEI-SPION triggered proinflammatory gene profiles in a murine endothelial cell line and in primary human umbilical cord vein endothelial cells (HUVECs). These nanoparticles impaired endothelial cell migration and inhibited HUVEC tube formation. Magnetically tumor-targeted PEI-SPIONs reduced tumor vessel numbers and promoted intratumor macrophage infiltration in a tumor xenograft model. PEI-SPION treatment impaired M2 macrophage-promoted tube formation and affected HUVEC cytoskeleton by limiting Src and Cortactin activation. These mechanisms could contribute to PEI-SPION in vitro and in vivo antiangiogenic potential. These data confirm that PEI-SPION administration and application of a localized magnetic field could offer an affordable anti-angiogenic anti-tumoral targeted treatment that would complement other therapies. Magnetically tumor-targeted polyethylenimine-coated superparamagnetic iron oxide nanoparticles impair in vitro and in vivo angiogenesis: PEI-SPIONs increase macrophage infiltration and reduce tumor vessel numbers in vivo. [Display omitted]