The protein corona formed on the surface of a nanoparticle in a biological medium determines its behavior in vivo. Herein, iron oxide nanoparticles containing the same core and shell, but bearing two ...different surface coatings, either glucose or poly(ethylene glycol), were evaluated. The nanoparticles’ protein adsorption, in vitro degradation, and in vivo biodistribution and biotransformation over four months were investigated. Although both types of nanoparticles bound similar amounts of proteins in vitro, the differences in the protein corona composition correlated to the nanoparticles biodistribution in vivo. Interestingly, in vitro degradation studies demonstrated faster degradation for nanoparticles functionalized with glucose, whereas the in vivo results were opposite with accelerated biodegradation and clearance of the nanoparticles functionalized with poly(ethylene glycol). Therefore, the variation in the degradation rate observed in vivo could be related not only to the molecules attached to the surface, but also with the associated protein corona, as the key role of the adsorbed proteins on the magnetic core degradation has been demonstrated in vitro.
Magnetic hyperthermia (MH) was used to treat a murine model of pancreatic cancer. This type of cancer is generally characterized by the presence of dense stroma that acts as a barrier for ...chemotherapeutic treatments. Several alternating magnetic field (AMF) conditions were evaluated using three-dimensional (3D) cell culture models loaded with magnetic nanoparticles (MNPs) to determine which conditions were producing a strong effect on the cell viability. Once the optimal AMF conditions were selected, in vivo experiments were carried out using similar frequency and field amplitude parameters. A marker of the immune response activation, calreticulin (CALR), was evaluated in cells from a xenograft tumor model after the MH treatment. Moreover, the distribution of nanoparticles within the tumor tissue was assessed by histological analysis of tumor sections, observing that the exposure to the alternating magnetic field resulted in the migration of particles toward the inner parts of the tumor. Finally, a relationship between an inadequate body biodistribution of the particles after their intratumoral injection and a significant decrease in the effectiveness of the MH treatment was found. Animals in which most of the particles remained in the tumor area after injection showed higher reductions in the tumor volume growth in comparison with those animals in which part of the particles were found also in the liver and spleen. Therefore, our results point out several factors that should be considered to improve the treatment effectiveness of pancreatic cancer by magnetic hyperthermia.
During the last decade, the possibility to remotely control intracellular pathways using physical tools has opened the way to novel and exciting applications, both in basic research and clinical ...applications. Indeed, the use of physical and non-invasive stimuli such as light, electricity or magnetic fields offers the possibility of manipulating biological processes with spatial and temporal resolution in a remote fashion. The use of magnetic fields is especially appealing for
applications because they can penetrate deep into tissues, as opposed to light. In combination with magnetic actuators they are emerging as a new instrument to precisely manipulate biological functions. This approach, coined as magnetogenetics, provides an exclusive tool to study how cells transform mechanical stimuli into biochemical signalling and offers the possibility of activating intracellular pathways connected to temperature-sensitive proteins. In this review we provide a critical overview of the recent developments in the field of magnetogenetics. We discuss general topics regarding the three main components for magnetic field-based actuation: the magnetic fields, the magnetic actuators and the cellular targets. We first introduce the main approaches in which the magnetic field can be used to manipulate the magnetic actuators, together with the most commonly used magnetic field configurations and the physicochemical parameters that can critically influence the magnetic properties of the actuators. Thereafter, we discuss relevant examples of magneto-mechanical and magneto-thermal stimulation, used to control stem cell fate, to activate neuronal functions, or to stimulate apoptotic pathways, among others. Finally, although magnetogenetics has raised high expectations from the research community, to date there are still many obstacles to be overcome in order for it to become a real alternative to optogenetics for instance. We discuss some controversial aspects related to the insufficient elucidation of the mechanisms of action of some magnetogenetics constructs and approaches, providing our opinion on important challenges in the field and possible directions for the upcoming years.
The field of nanotechnology applied to medicine (nanomedicine) is developing at a fast pace and is expected to provide solutions for early diagnosis, targeted therapy, and personalized medicine. ...However, designing nanomaterials for biomedical applications is not a trivial task. Avoidance of the immune system, stability in physiological media, control over the interaction of a nanomaterial with biological entities such as proteins and cell membranes, low toxicity, and optimal bioperformance are critical for the success of the designed nanomaterial. In this Feature Article we provide a concise overview of some of the most recent advances concerning the derivatization of gold and iron oxide nanoparticles for bioapplications. The most important aspects relating to the functionalization of gold and iron oxide nanoparticles with carbohydrates, peptides, nucleic acids, and antibodies are covered, highlighting the recent contributions from our research group. We suggest tips for the appropriate (bio)functionalization of these inorganic nanoparticles in order to preserve the biological activity of the attached biomolecules and ensure their subsequent stability in physiological media.
High aspect ratio magnetic nanomaterials possess anisotropic properties that make them attractive for biological applications. Their elongated shape enables multivalent interactions with receptors ...through the introduction of multiple targeting units on their surface, thus enhancing cell internalization. Moreover, due to their magnetic anisotropy, high aspect ratio nanomaterials can outperform their spherical analogues as contrast agents for magnetic resonance imaging (MRI) applications. In this review, we first describe the two main synthetic routes for the preparation of anisotropic magnetic nanomaterials: (i) direct synthesis (in which the anisotropic growth is directed by tuning the reaction conditions or by using templates) and (ii) assembly methods (in which the high aspect ratio is achieved by assembly from individual building blocks). We then provide an overview of the biomedical applications of anisotropic magnetic nanomaterials: magnetic separation and detection, targeted delivery and magnetic resonance imaging.
Magnetic nanoparticles (MNPs) are promising tools for a wide array of biomedical applications. One of their most outstanding properties is the ability to generate heat when exposed to alternating ...magnetic fields, usually exploited in magnetic hyperthermia therapy of cancer. In this contribution, we provide a critical review of the use of MNPs and magnetic hyperthermia as drug release and gene expression triggers for cancer therapy. Several strategies for the release of chemotherapeutic drugs from thermo-responsive matrices are discussed, providing representative examples of their application at different levels (from proof of concept to in vivo applications). The potential of magnetic hyperthermia to promote in situ expression of therapeutic genes using vectors that contain heat-responsive promoters is also reviewed in the context of cancer gene therapy.
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•Thermal decomposition by successive additions allows obtaining magnetite particles of 11–23 nm.•Preparation of water souble NPs by recovering with PMAO, DMSA and TESPMA ...ligands.•Fe3O4@PMAO nanoparticles display high values of SAR, increasing with the size of the NP.•RGD peptides have been targeted to Fe3O4@PMAO NPs by “click” chemistry.•Fe3O4@PMAO@PEG/RGD NPs exhibit nontoxicity in “in vitro” assays.
To improve the selectivity of magnetic nanoparticles for tumor treatment by hyperthermia, Fe3O4 nanoparticles have been functionalized with a peptide of the type arginine-glycine-aspartate (RGD) following a “click” chemistry approach. The RGD peptide was linked onto the previously coated nanoparticles in order to target αvβ3 integrin receptors over-expressed in angiogenic cancer cells. Different coatings have been analyzed to enhance the biocompatibility of magnetic nanoparticles. Monodispersed and homogeneous magnetite nanoparticles have been synthesized by the seed growth method and have been characterized using X-ray diffraction, thermogravimetric analysis, infrared spectroscopy, transmission electron microscopy and magnetic measurements. The magnetic hyperthermia efficiency of the nanoparticles has also been investigated and cytotoxicity assays have been perfomed for functionalized nanoparticles.
Nuclear magnetic resonance (NMR) spectroscopy is one of the most information-rich analytical techniques available. However, it is also inherently insensitive, and this drawback precludes the ...application of NMR spectroscopy to mass- and volume-limited samples. We review a particular approach to increase the sensitivity of NMR experiments, namely the use of miniaturized coils. When the size of the coil is reduced, the sample volume can be brought down to the nanoliter range. We compare the main coil geometries (solenoidal, planar, and microslot/stripline) and discuss their applications to the analysis of mass-limited samples. We also provide an overview of the hyphenation of microcoil NMR spectroscopy to separation techniques and of the integration with lab-on-a-chip devices and microreactors.
Monitoring extracellular matrix (ECM) components is one of the key methods used to determine tissue quality in three-dimensional (3D) scaffolds for regenerative medicine and clinical purposes. This ...is even more important when multipotent human bone marrow stromal cells (hMSCs) are used, as it could offer a method to understand in real time the dynamics of stromal cell differentiation and eventually steer it into the desired lineage. Magnetic Resonance Imaging (MRI) is a promising tool to overcome the challenge of a limited transparency in opaque 3D scaffolds. Technical limitations of MRI involve non-uniform background intensity leading to fluctuating background signals and therewith complicating quantifications on the retrieved images. We present a post-imaging processing sequence that is able to correct for this non-uniform background intensity. To test the processing sequence we investigated the use of MRI for in vitro monitoring of tissue growth in three-dimensional poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) scaffolds. Results showed that MRI, without the need to use contrast agents, is a promising non-invasive tool to quantitatively monitor ECM production and cell distribution during in vitro culture in 3D porous tissue engineered constructs.
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