Abstract
This work reports important advances in the study of magnetic nanoparticles (MNPs) related to their application in different research fields such as magnetic hyperthermia. Nanotherapy based on targeted nanoparticles could become an attractive alternative to conventional oncologic treatments as it allows a local heating in tumoral surroundings without damage to healthy tissue. RGD-peptide-conjugated MNPs have been designed to specifically target αVβ3 receptor-expressing cancer cells, being bound the RGD peptides by “click chemistry” due to its selectivity and applicability. The thermal decomposition of iron metallo-organic precursors yield homogeneous Fe3O4 nanoparticles that have been properly functionalized with RGD peptides, and the preparation of magnetic fluids has been achieved. The nanoparticles were characterized by transmission electron microscopy (TEM), vibrating sample magnetometry (VSM), electron magnetic resonance (EMR) spectroscopy and magnetic hyperthermia. The nanoparticles present superparamagnetic behavior with very high magnetization values, which yield hyperthermia values above 500 W/g for magnetic fluids. These fluids have been administrated to rats, but instead of injecting MNP fluid directly into liver tumors, intravascular administration of MNPs in animals with induced colorectal tumors has been performed. Afterwards the animals were exposed to an alternating magnetic field in order to achieve hyperthermia. The evolution of an in vivo model has been described, resulting in a significant reduction in tumor viability.
Highlights
Colorectal liver metastases are still a challenge for surgeons and oncologists
The method of thermal decomposition by successive additions allowed the synthesis of magnetite nanoparticles surrounded by oleic acid (Fe3O4@OA), which have been transferred to water by an amphiphilic ligand, becoming hydrosoluble nanoparticles (Fe3O4@PMAO)
Carboxylic groups of PMAO were anchored with an amino-modified linker to add an alkyne group, which are the alkyne-modified NPs coupled by the azide-modified RGD peptide (RGD-N3) in water in a one-step procedure by a click reaction (Fe3O4@PMAO_RGD)
Summary
Colorectal liver metastases are still a challenge for surgeons and oncologists. Though surgical removal of the metastases is currently the best therapeutic option, it is only indicated in less than 50% of the patients. The ultimate goal would be to deliver enough of these RGD-functionalized MNPs through the hepatic artery to the connective tissue around the liver metastases in order to achieve a local thermal increase to destroy the vessels and hinder tumor progression. The zeta potential value at 24 h confirms the high stability of the aqueous solutions of Fe3O4@PMAO (−41 mV), but the stability decreases until −15 mV when RGD is adhered to the NPs. Infrared spectra of the magnetic nanoparticles have been performed in order to determine the type of ligands surrounding the magnetic nuclei (see Supporting Information File 1, Figure S2).
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