M. Ricardo Ibarra

Magnetic nanoparticles for drug delivery

Controlled release of drugs from nanostructured functional materials, especially nanoparticles (NPs), is attracting increasing attention because of the opportunities in cancer therapy and the treatment of other ailments. The potential of magnetic NPs stems from the intrinsic properties of their magnetic cores combined with their drug loading capability and the biochemical properties that can be bestowed on them by means of a suitable coating. Here we review the problems and recent advances in the development of magnetic NPs for drug delivery, focusing particularly on the materials involved.

Nanoparticle penetration and transport in living pumpkin plants: in situ subcellular identification

BackgroundIn recent years, the application of nanotechnology in several fields of bioscience and biomedicine has been studied. The use of nanoparticles for the targeted delivery of substances has been given special attention and is of particular interest in the treatment of plant diseases. In this work both the penetration and the movement of iron-carbon nanoparticles in plant cells have been analyzed in living plants of Cucurbita pepo.ResultsThe nanoparticles were applied in planta using two different application methods, injection and spraying, and magnets were used to retain the particles in movement in specific areas of the plant. The main experimental approach, using correlative light and electron microscopy provided evidence of intracellular localization of nanoparticles and their displacement from the application point. Long range movement of the particles through the plant body was also detected, particles having been found near the magnets used to immobilize and concentrate them. Furthermore, cell response to the nanoparticle presence was detected.ConclusionNanoparticles were capable of penetrating living plant tissues and migrating to different regions of the plant, although movements over short distances seemed to be favoured. These findings show that the use of carbon coated magnetic particles for directed delivery of substances into plant cells is a feasible application.

Assessing Methods for Blood Cell Cytotoxic Responses to Inorganic Nanoparticles and Nanoparticle Aggregates

Inorganic nanoparticles (NPs) show great potential for medicinal therapy. However, biocompatibility studies are essential to determine if they are safe. Here, five different NPs are compared for their cytotoxicity, internalization, aggregation in medium, and reactive oxygen species (ROS) production, using tumoral and normal human blood cells. Differences depending on the cell type are analyzed, and no direct correlation between ROS production and cell toxicity is found. Results are discussed with the aim of standardizing the procedures for the evaluation of the toxicity.

In vivo tumor targeting via nanoparticle-mediated therapeutic siRNA coupled to inflammatory response in lung cancer mouse models

Up to now, functionalized gold nanoparticles have been optimized as an effective intracellular in vitro delivery vehicle for siRNAs to interfere with the expression of specific genes by selective targeting, and provide protection against nucleases. Few examples however of suchlike in vivo applications have been described so far. In this study, we report the use of siRNA/RGD gold nanoparticles capable of targeting tumor cells in a lung cancer syngeneic orthotopic murine model. Therapeutic RGD-nanoparticle treatment resulted in successful targeting evident from significant c-myc oncogene down-regulation followed by tumor growth inhibition and prolonged survival of lung tumor bearing mice, possibly via αvβ3 integrin interaction. Our results suggest that RGD gold nanoparticles-mediated delivery of siRNA by intratracheal instillation in mice leads to successful suppression of tumor cell proliferation and respective tumor size reduction. These results reiterate the capability of functionalized gold nanoparticles for targeted delivery of siRNA to cancer cells towards effective silencing of the specific target oncogene. What is more, we demonstrate that the gold-nanoconjugates trigger a complex inflammatory and immune response that might promote the therapeutic effect of the RNAi to reduce tumor size with low doses of siRNA.

Three dimensional magnetic nanowires grown by focused electron-beam induced deposition.

Control of the motion of domain walls in magnetic nanowires is at the heart of various recently proposed three-dimensional (3D) memory devices. However, fabricating 3D nanostructures is extremely complicated using standard lithography techniques. Here we show that highly pure 3D magnetic nanowires with aspect-ratios of ~100 can be grown using focused electron-beam-induced-deposition. By combining micromanipulation, Kerr magnetometry and magnetic force microscopy, we determine that the magnetisation reversal of the wires occurs via the nucleation and propagation of domain walls. In addition, we demonstrate that the magnetic switching of individual 3D nanostructures can be directly probed by magneto-optical Kerr effect.

Absorption and translocation to the aerial part of magnetic carbon-coated nanoparticles through the root of different crop plants

The development of nanodevices for agriculture and plant research will allow several new applications, ranging from treatments with agrochemicals to delivery of nucleic acids for genetic transformation. But a long way for research is still in front of us until such nanodevices could be widely used. Their behaviour inside the plants is not yet well known and the putative toxic effects for both, the plants directly exposed and/or the animals and humans, if the nanodevices reach the food chain, remain uncertain. In this work we show that magnetic carbon-coated nanoparticles forming a biocompatible magnetic fluid (bioferrofluid) can easily penetrate through the root in four different crop plants (pea, sunflower, tomato and wheat). They reach the vascular cylinder, move using the transpiration stream in the xylem vessels and spread through the aerial part of the plants in less than 24 hours. Accumulation of nanoparticles was detected in wheat leaf trichomes, suggesting a way for excretion/detoxification. This kind of studies is of great interest in order to unveil the movement and accumulation of nanoparticles in plant tissues for assessing further applications in the field or laboratory.

Magnetic nanoparticles for local drug delivery using magnetic implants

Magnetic nanoparticles are good candidates used for the targeted delivery of anti-tumor agents. They can be concentrated on a desired region, reducing collateral effects and improving the efficiency of the chemotherapy. We propose a method in which permanent magnets are implanted by laparoscopic technique directly in the affected organ. This method proposes the use of Fe@C nanoparticles, which are loaded with doxorubicin and injected intravenously. The particles, once attracted to the magnet, release the drug at the tumor region. This method seems to be more promising and effective than that based on the application of external magnetic fields.

Cell death induced by AC magnetic fields and magnetic nanoparticles: current state and perspectives.

Abstract This review analyses the advances in the field of magnetically induced cell death using intracellular magnetic nanoparticles (MNPs). Emphasis has been given to in vitro research results, discussing the action of radiofrequency (RF) waves on biological systems as well as those results of thermally induced cell death in terms of MNP cell interactions. Our main goal has been to provide a unified depiction of many recent experiments and theoretical models relevant to the effect of applied electromagnetic fields on MNPs after cellular uptake and the cytotoxicity assessment of MNPs. We have addressed the effects of RF waves used for in vitro magnetic hyperthermia on eukaryotic cells regarding physical modifications of the cellular local environment and cell viability.

Tailored design of CoxMn1−xFe2O4 nanoferrites: a new route for dual control of size and magnetic properties

This work reports the tailored design of novel mixed ferrite nanoparticles, CoxMn1−xFe2O4 (x = 0, 0.3, 0.7, and 1), through an optimized one-pot aqueous coprecipitation process. The influence of the substitution between Mn(II) and Co(II) and of the alkaline agent, isopropanolamine (MIPA) or NaOH, on the morphological, chemical and magnetic properties of the nanomaterials was investigated. The joint action between chemical substitution and type of alkaline agent allowed a precise tuning of the particle size, magnetic properties and inversion degree of the spinel structure. A wide range of particle dimensions (from 3 to 30 nm) and saturation magnetization (from 57 to 71 emu g−1) was achieved. The increase of Co(II) content from x = 0 to x = 1 led to a systematic decrease of the particle size, regardless of the base type, which could be modelled by an exponential decay function. For each Co:Mn composition, the use of MIPA instead of the traditional NaOH promoted a three times reduction of the particle size and simultaneously switched the magnetic state of the CoxMn1−xFe2O4 nanomaterials from ferromagnetic to superparamagnetic. These results constitute a step forward in the challenging quest for high-performance magnetic nanoprobes by an eco-friendly synthesis route.

Neuronal cells loaded with PEI-coated Fe3O4 nanoparticles for magnetically guided nerve regeneration

We report a one-step synthesis protocol for obtaining polymer-coated magnetic nanoparticles (MNPs) engineered for uploading neural cells. Polyethyleneimine-coated Fe3O4 nanoparticles (PEI-MNPs) with sizes of 25 ± 5 nm were prepared by oxidation of Fe(OH)2 by nitrate in basic aqueous media and adding PEI in situ during synthesis. The obtained PEI-MNP cores displayed a neat octahedral morphology and high crystallinity. The resulting nanoparticles were coated with a thin polymer layer of about 0.7-0.9 nm, and displayed a saturation magnetization value MS = 58 A m2 kg-1 at 250 K (64 A m2 kg-1 for T = 10 K). Cell uptake experiments on a neuroblastoma-derived SH-SY5Y cell line were undertaken over a wide time and MNP concentration range. The results showed a small decrease in cell viability for 24 h incubation (down to 70% viability for 100 μg ml-1), increasing the toxic effects with incubation time (30% cell survival at 100 μg ml-1 for 7 days of incubation). On the other hand, primary neuronal cells displayed higher sensitivity to PEI-MNPs, with a cell viability reduction of 44% of the control cells after 3 days of incubation with 50 μg ml-1. The amount of PEI-MNPs uploaded by SH-SY5Y cells was found to have a linear dependence on concentration. The intracellular distribution of the PEI-MNPs analyzed at the single-cell level by the dual-beam (FIB/SEM) technique revealed the coexistence of both fully incorporated PEI-MNPs and partially internalized PEI-MNP-clusters crossing the cell membrane. The resulting MNP-cluster distributions open the possibility of using these PEI-MNPs for magnetically driven axonal re-growth in neural cells.