Abstract
Iron oxide nanoparticles (NPs) have been proposed for many biomedical applications as in vivo imaging and drug delivery in cancer treatment, but their toxicity is an ongoing concern. When NPs are intravenously administered, the endothelium represents the first barrier to tissue diffusion/penetration. However, there is little information about the biological effects of NPs on endothelial cells. In this work we showed that cobalt-ferrite (CoFe2O4) NPs affect endothelial cell integrity by increasing permeability, oxidative stress, inflammatory profile and by inducing cytoskeletal modifications. To overcome these problems, NPs have be loaded into biocompatible gels to form nanocomposite hybrid material (polysaccharide hydrogels containing magnetic NPs) that can be further conjugated with anticancer drugs to allow their release close to the target. The organic part of hybrid biomaterials is a carboxymethylcellulose (CMC) polymer, while the inorganic part consists of CoFe2O4 NPs coated with (3-aminopropyl)trimethoxysilane. The biological activity of these hybrid hydrogels was evaluated in vitro and in vivo. Our findings showed that hybrid hydrogels, instead of NPs alone, were not toxic on endothelial, stromal and epithelial cells, safe and biodegradable in vivo. In conclusion, biohydrogels with paramagnetic NPs as cross-linkers can be further exploited for antitumor drug loading and delivery systems.
Highlights
Magnetic iron oxide nanoparticles (NPs) have been widely investigated for many years
To understand the impact of NPs on vascular integrity, we investigated their activity on endothelial cells in vitro
In view of these results, to investigate the mechanisms underlying reduction in endothelial cell number and survival, we analysed some molecular pathways in cells activated after treatment with the different NPs, focusing on the pro-apoptotic signal caspase-3 and proteins involved in cell cycle regulation
Summary
Magnetic iron oxide nanoparticles (NPs) have been widely investigated for many years. Due to their magnetic, electronic and optical properties, they are good candidates for future use in biomedical practice. Several applications have been proposed, as diagnostic tests, in vivo imaging, targeted drug delivery and tissue regeneration [1, 2]. Superparamagnetic iron oxide NPs (SPIONs), as cobalt ferrite NPs, have been developed for magnetic resonance imaging (MRI), magnetic intracellular/interstitial hyperthermia and magnetic drug targeting, they are proposed both as therapeutic and theranostic agents [3] and at the present big efforts are conducted to develop clinically relevant drug delivery systems.
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