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1.
Pharmaceutics ; 14(8)2022 Jul 22.
Article in English | MEDLINE | ID: mdl-35893782

ABSTRACT

The clinical implementation of magnetic hyperthermia has experienced little progress since the first clinical trial was completed in 2005. Some of the hurdles to overcome are the reliable production of magnetic nanoparticles with controlled properties and the control of the temperature at the target tissue in vivo. Here, forty samples of iron oxide superparamagnetic nanoparticles were prepared by similar methods and thoroughly characterized in terms of size, aggregation degree, and heating response. Selected samples were intratumorally administered in animals with subcutaneous xenografts of human pancreatic cancer. In vivo experiments showed that it is possible to control the rise in temperature by modulating the field intensity during in vivo magnetic hyperthermia protocols. The procedure does not require sophisticated materials and it can be easily implemented by researchers or practitioners working in magnetic hyperthermia therapies.

2.
Cancers (Basel) ; 13(16)2021 Aug 14.
Article in English | MEDLINE | ID: mdl-34439250

ABSTRACT

Magnetic nanoparticles (MNP) are employed as nanocarriers and in magnetic hyperthermia (MH) for the treatment of cancers. Herein, a smart drug delivery system composed of MNP functionalized with the cytotoxic drug gemcitabine (MNP-GEM) has been thoroughly evaluated. The linker employed is based on a disulfide bond and allows the controlled release of GEM under a highly reducing environment, which is frequently present in the cytoplasm of tumor cells. The stability, MH, and the interaction with plasma proteins of the nanoparticles are evaluated, highlighting their great potential for biological applications. Their cytotoxicity is assessed in three pancreatic cancer cell lines with different sensitivity to GEM, including the generation of reactive oxygen species (ROS), the effects on the cell cycle, and the mechanisms of cell death involved. Remarkably, the proposed nanocarrier is better internalized than unmodified nanoparticles, and it is particularly effective in PANC-1 cells, resistant to GEM, but not in non-tumoral keratinocytes. Additionally, its combination with MH produces a synergistic cytotoxic effect in all cancer cell lines tested. In conclusion, MNP-GEM presents a promising potential for treating pancreatic cancer, due to multiple parameters, such as reduced binding to plasma proteins, increased internalization, and synergistic activity when combined with MH.

3.
Colloids Surf B Biointerfaces ; 194: 111178, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32531715

ABSTRACT

The antibacterial activity of hybrid γ-Fe2O3/Ag nanocomposites against the bacterial pathogens E. coli (Gram-negative) and S. aureus (Gram-positive) has been studied. Silver is a well-known bactericidal agent and γ-Fe2O3 nanoparticles release heat when they are exposed to alternating magnetic fields. The combination of both properties to fight infections has not been previously explored. The nanocomposites were synthesized through reduction of silver nitrate in the presence of pre-synthesized superparamagnetic γ-Fe2O3 nanoparticles. Changing systematically the ratio of γ-Fe2O3 and silver precursor and the temperature of the reaction allowed obtaining superparamagnetic nanocomposites with different Ag contents and particle sizes. The antibacterial activity of the samples was tested, and the minimum inhibitory concentrations and minimum bactericidal concentrations of the nanocomposites were determined to compare the microbicidal activity of the samples. It was found that it is related with the release of silver ions from the nanocomposites. Finally, we studied the combination of the bactericidal effect of silver and magnetic hyperthermia finding a synergetic effect between them when plates containing E. coli or S. aureus bacteria with γ-Fe2O3/Ag nanocomposites were subjected to an alternating magnetic field. This effect is related with an increase in the release of silver ions due to that heat dissipation.


Subject(s)
Metal Nanoparticles , Nanocomposites , Anti-Bacterial Agents/pharmacology , Escherichia coli , Microbial Sensitivity Tests , Silver/pharmacology , Staphylococcus aureus
4.
Bioconjug Chem ; 27(11): 2734-2743, 2016 Nov 16.
Article in English | MEDLINE | ID: mdl-27809485

ABSTRACT

Design of generic methods aimed at the oriented attachment of proteins at the interfacial environment of magnetic nanoparticles currently represents an active field of research. With this in mind, we have prepared and characterized agarose-coated maghemite nanoparticles to set up a platform for the attachment of recombinant proteins fused to the ß-trefoil lectin domain LSL150, a small protein that combines fusion tag properties with agarose-binding capacity. Analysis of the agarose-coated nanoparticles by dynamic light scattering, Fourier transform infrared spectroscopy, and thermogravimetric studies shows that decoupling particle formation from agarose coating provides better results in terms of coating efficiency and particle size distribution. LSL150 interacts with these agarose-coated nanoparticles exclusively through the recognition of the sugars of the polymer, forming highly stable complexes, which in turn can be dissociated ad hoc with the competing sugar lactose. Characterization of the complexes formed with the fusion proteins LSL-EGFP (LSL-tagged enhanced green fluorescent protein from Aquorea victoria) and LSL-BTL2 (LSL-tagged lipase from Geobacillus thermocatenolatus) provided evidence supporting a topologically oriented binding of these molecules to the interface of the agarose-coated nanoparticles. This is consistent with the marked polarity of the ß-trefoil structure where the sugar-binding sites and the N- and C-terminus ends are at opposed sides. In summary, LSL150 displays topological and functional features expected from a generic molecular adaptor for the oriented attachment of proteins at the interface of agarose-coated nanoparticles.


Subject(s)
Ferric Compounds/chemistry , Lotus/chemistry , Nanoparticles/chemistry , Plant Lectins/chemistry , Recombinant Fusion Proteins/chemistry , Sepharose/chemistry , Models, Molecular , Protein Domains
5.
Nanotechnology ; 26(20): 205101, 2015 May 22.
Article in English | MEDLINE | ID: mdl-25927227

ABSTRACT

Iron oxide nanoparticles with engineered physical and biochemical properties are finding a rapidly increasing number of biomedical applications. However, a wide variety of safety concerns, especially those related to oral exposure, still need to be addressed for iron oxide nanoparticles in order to reach clinical practice. Here, we report on the effects of chronic oral exposure to low doses of γ-Fe2O3 nanoparticles in growing chickens. Animal observation, weight, and diet intake reveal no adverse signs, symptoms, or mortality. No nanoparticle accumulation was observed in liver, spleen, and duodenum, with feces as the main excretion route. Liver iron level and duodenal villi morphology reflect the bioavailability of the iron released from the partial transformation of γ-Fe2O3 nanoparticles in the acid gastric environment. Duodenal gene expression studies related to the absorption of iron from γ-Fe2O3 nanoparticles indicate the enhancement of a ferric over ferrous pathway supporting the role of mucins. Our findings reveal that oral administration of iron oxide nanoparticles is a safe route for drug delivery at low nanoparticle doses.


Subject(s)
Ferric Compounds/toxicity , Metal Nanoparticles/toxicity , Administration, Oral , Animals , Body Weight/drug effects , Chickens , Duodenum/drug effects , Duodenum/metabolism , Duodenum/pathology , Eating/drug effects , Ferric Compounds/metabolism , Ferric Compounds/pharmacokinetics , Gene Expression/drug effects , Iron/metabolism
6.
Nanomedicine ; 10(4): 733-43, 2014 May.
Article in English | MEDLINE | ID: mdl-24333592

ABSTRACT

We have performed a series of in vitro tests proposed for the reliable assessment of safety associated with nanoparticles-cell interaction. A thorough analysis of toxicity of three different coating iron oxide nanoparticles on HeLa cells has been carried out including, methyl thiazol tetrazolium bromide (MTT) and Trypan blue exclusion tests, cell morphology observation by optical and Scanning Electron Microscopy (SEM), study of cytoskeletal components, analysis of cell cycle and the presence of reactive oxygen species (ROS). We have quantified magnetic nanoparticle internalization, determined possible indirect cell damages and related it to the nanoparticle coating. The results confirm a very low toxicity of the analyzed iron oxide nanoparticles into HeLa cells by multiple assays and pave the way for a more successful cancer diagnostic and treatment without secondary effects. FROM THE CLINICAL EDITOR: In this paper, three different iron oxide nanoparticles are studied and compared from the standpoint of safety and toxicity in HeLa cells, demonstrating low toxicity for each preparation, and paving the way to potential future clinical applications.


Subject(s)
Ferric Compounds , Magnetite Nanoparticles/chemistry , Cytoskeleton/metabolism , Cytoskeleton/ultrastructure , Ferric Compounds/chemistry , Ferric Compounds/pharmacology , HeLa Cells , Humans , Magnetite Nanoparticles/ultrastructure , Reactive Oxygen Species/metabolism
7.
Nanoscale ; 5(23): 11428-37, 2013 Dec 07.
Article in English | MEDLINE | ID: mdl-23963338

ABSTRACT

Recent advances in nanotechnology have permitted the development of a wide repertoire of inorganic magnetic nanoparticles (NPs) with extensive promise for biomedical applications. Despite this remarkable potential, many questions still arise concerning the biocompatible nature of NPs when in contact with biological systems. Herein, we have investigated how controlled changes in the physicochemical properties of iron oxide NPs at their surface (i.e., surface charge and hydrodynamic size) affect, first, their interaction with cell media components and, subsequently, cell responses to NP exposure. For that purpose, we have prepared iron oxide NPs with three different coatings (i.e., dimercaptosuccinic acid - DMSA, (3-aminopropyl)triethoxysilane - APS and dextran) and explored the response of two different cell types, murine L929 fibroblasts and human Saos-2 osteoblasts, to their exposure. Interestingly, different cell responses were found depending on the NP concentration, surface charge and cell type. In this sense, neutral NPs, as those coated with dextran, induced negligible cell damage, as their cellular internalization was significantly reduced. In contrast, surface-charged NPs (i.e., those coated with DMSA and APS) caused significant cellular changes in viability, morphology and cell cycle under certain culture conditions, as a result of a more active cellular internalization. These results also revealed a particular cellular ability to detect and remember the original physicochemical properties of the NPs, despite the formation of a protein corona when incubated in culture media. Overall, conclusions from these studies are of crucial interest for future biomedical applications of iron oxide NPs.


Subject(s)
Ferric Compounds/chemistry , Metal Nanoparticles/chemistry , Animals , Cell Cycle Checkpoints/drug effects , Cell Line , Cell Survival/drug effects , Dextrans/chemistry , Humans , Metal Nanoparticles/toxicity , Mice , Microscopy, Confocal , Particle Size , Propylamines/chemistry , Silanes/chemistry , Succimer/chemistry , Surface Properties
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