Injectable formulations forming an implant in situ as vehicle of silica microparticles embedding superparamagnetic iron oxide nanoparticles for the local, magnetically mediated hyperthermia treatment of solid tumors (original) (raw)
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Biomaterials, 2010
We investigated the use of in situ implant formation that incorporates superparamagnetic iron oxide nanoparticles (SPIONs) as a form of minimally invasive treatment of cancer lesions by magnetically induced local hyperthermia. We developed injectable formulations that form gels entrapping magnetic particles into a tumor. We used SPIONs embedded in silica microparticles to favor syringeability and incorporated the highest proportion possible to allow large heating capacities. Hydrogel, single-solvent organogel and cosolvent (low-toxicity hydrophilic solvent) organogel formulations were injected into human cancer tumors xenografted in mice. The thermoreversible hydrogels (poloxamer, chitosan), which accommodated 20% w/v of the magnetic microparticles, proved to be inadequate. Alginate hydrogels, however, incorporated 10% w/v of the magnetic microparticles, and the external gelation led to strong implants localizing to the tumor periphery, whereas internal gelation failed in situ. The organogel formulations, which consisted of precipitating polymers dissolved in single organic solvents, displayed various microstructures. A 8% poly(ethylene-vinyl alcohol) in DMSO containing 40% w/v of magnetic microparticles formed the most suitable implants in terms of tumor casting and heat delivery. Importantly, it is of great clinical interest to develop cosolvent formulations with up to 20% w/v of magnetic microparticles that show reduced toxicity and centered tumor implantation.
Journal of Magnetism and Magnetic Materials, 2011
The biological and therapeutic responses to hyperthermia, when it is envisaged as an anti-tumor treatment modality, are complex and variable. Heat delivery plays a critical role and is counteracted by more or less efficient body cooling, which is largely mediated by blood flow. In the case of magnetically mediated modality, the delivery of the magnetic particles, most often superparamagnetic iron oxide nanoparticles (SPIONs), is also critically involved. We focus here on the magnetic characterization of two injectable formulations able to gel in situ and entrap silica microparticles embedding SPIONs. These formulations have previously shown suitable syringeability and intratumoral distribution in vivo. The first formulation is based on alginate, and the second on a poly(ethylene-co-vinyl alcohol) (EVAL). Here we investigated the magnetic properties and heating capacities in an alternating magnetic field (141 kHz, 12 mT) for implants with increasing concentrations of magnetic microparticles. We found that the magnetic properties of the magnetic microparticles were preserved using the formulation and in the wet implant at 37 1C, as in vivo. Using two orthogonal methods, a common SLP (20 W g À 1 ) was found after weighting by magnetic microparticle fraction, suggesting that both formulations are able to properly carry the magnetic microparticles in situ while preserving their magnetic properties and heating capacities.
In this chapter we review both preformulation and formulation efforts relevant to magnetically-induced hyperthermia as a new and attractive modality for the treatment of cancer lesions eligible for a thermotherapy. Also addressed are the efforts to apply this method to de novo indications in specific clinical situations. Following a pharmaceutical approach, we first introduce the general biological rationale for the use of hyperthermia, considering the techniques available to generate hyperthermia. We then detail several different magnetically-induced heating modalities and review the literature on formulations in an attempt to compare their specificities, advantages and shortcomings. First, we consider the formulation of glass ceramics and cement biomaterials for magnetically mediated hyperthermia with respect to the biological specificities in the treatment of solid bone tumors. Secondly, formulations intended for magnetically mediated hyperthermia are considered for soft tissue solid tumors, emphasizing the potential for pharmacological modulation. In the final section, we consider magnetic liposome formulations that can be equally administrated in various types of tumors. We do not detail magnetic fluid hyperthermia that uses suspensions of magnetic nanoparticles stabilized by various coatings. Biological and immunological considerations revealed by liposomes are outlined. This chapter focuses on the importance of the formulation and on
Small versus Large Iron Oxide Magnetic Nanoparticles: Hyperthermia and Cell Uptake Properties
Molecules, 2016
Efficient use of magnetic hyperthermia in clinical cancer treatment requires biocompatible magnetic nanoparticles (MNPs), with improved heating capabilities. Small (~34 nm) and large (~270 nm) Fe 3 O 4-MNPs were synthesized by means of a polyol method in polyethylene-glycol (PEG) and ethylene-glycol (EG), respectively. They were systematically investigated by means of X-ray diffraction, transmission electron microscopy and vibration sample magnetometry. Hyperthermia measurements showed that Specific Absorption Rate (SAR) dependence on the external alternating magnetic field amplitude (up to 65 kA/m, 355 kHz) presented a sigmoidal shape, with remarkable SAR saturation values of~1400 W/g MNP for the small monocrystalline MNPs and only 400 W/g MNP for the large polycrystalline MNPs, in water. SAR values were slightly reduced in cell culture media, but decreased one order of magnitude in highly viscous PEG1000. Toxicity assays performed on four cell lines revealed almost no toxicity for the small MNPs and a very small level of toxicity for the large MNPs, up to a concentration of 0.2 mg/mL. Cellular uptake experiments revealed that both MNPs penetrated the cells through endocytosis, in a time dependent manner and escaped the endosomes with a faster kinetics for large MNPs. Biodegradation of large MNPs inside cells involved an all-or-nothing mechanism.
International Journal of Nanomedicine Intravenous magnetic nanoparticle cancer hyperthermia
Magnetic nanoparticles heated by an alternating magnetic field could be used to treat cancers, either alone or in combination with radiotherapy or chemotherapy. However, direct intratumoral injections suffer from tumor incongruence and invasiveness, typically leaving undertreated regions, which lead to cancer regrowth. Intravenous injection more faithfully loads tumors, but, so far, it has been difficult achieving the necessary concentration in tumors before systemic toxicity occurs. Here, we describe use of a magnetic nanoparticle that, with a well-tolerated intravenous dose, achieved a tumor concentration of 1.9 mg Fe/g tumor in a subcutaneous squamous cell carcinoma mouse model, with a tumor to non-tumor ratio . 16. With an applied field of 38 kA/m at 980 kHz, tumors could be heated to 60°C in 2 minutes, durably ablating them with millimeter (mm) precision, leaving surrounding tissue intact.
Magnetism for Drug Delivery, MRI and Hyperthermia Applications: a Review
2020
Superparamagnetic nanoparticles contain unique magnetic properties that differ from the bulk materials and are able to function at a cellular level due to their size, shape, and surface characteristics. These features make them attractive candidates for drug delivery systems, thermal mediators in hyperthermia, and magnetic resonance imaging (MRI) contrast agents. This review provides an up-to-date overview of the application of iron oxide nanoparticles in cancer diagnosis, drug delivery, treatment, and safety concerns related to these materials are considered, as well. Furthermore, the general principles and challenges of the magnetic behavior of nanoparticles in the field of oncology are also discussed. Firstly, the basic requirements for magnetic nanoparticles for biomedical applications are outlined. The close link between structure, shape, size, and magnetic characterization are described, which is considered essential for non-invasive imaging modality, innovative magneticdriven...
IRON OXIDE NANOPARTICLES AS THERMAL SEEDS IN MAGNETIC HYPERTHERMIA THERAPY
we present the short review on Magnetic nanoparticle specifically for biomedical application. This study shows the overview on magnetic material properties and its biocompatibility. Here we are discussing some results of manufacturing iron nano particle in lab and its thermal propertie srelated to hyperthermia. Keywords-Magnetic nanoparticle (MNP).
ACS Applied Materials & Interfaces, 2018
In this study, we present an innovation in the tumor treatment in vivo mediated by magnetic mesoporous silica nanoparticles. This device was built with iron oxide magnetic nanoparticles embedded in a mesoporous silica matrix and coated with an engineered thermoresponsive polymer. The magnetic nanoparticles act as internal heating sources under an alternating magnetic field (AMF) that increase the temperature of the surroundings, provoking the polymer transition and consequently the release of a drug trapped inside the silica pores. By a synergic effect between the intracellular hyperthermia and chemotherapy triggered by AMF application, significant tumor growth inhibition was achieved in 48 h after treatment. Furthermore, the small magnetic loading used in the experiments indicates that the treatment is carried out without a global temperature rise of the tissue, which avoids the problem of the necessity to employ large amounts of magnetic cores, as is common in current magnetic hyperthermia.
International Journal of Molecular Sciences
In this study, we developed iron oxide nanoparticles stabilised with oleic acid/sodium oleate that could exert therapeutic effects for curing tumours via magnetic hyperthermia. A suspension of iron oxide nanoparticles was produced and characterised. The toxicity of the synthesised composition was examined in vivo and found to be negligible. Histological examination showed a low local irritant effect and no effect on the morphology of the internal organs. The efficiency of magnetic hyperthermia for the treatment of transplanted Walker 256 carcinoma was evaluated. The tumour was infiltrated with the synthesised particles and then treated with an alternating magnetic field. The survival rate was 85% in the studied therapy group of seven animals, while in the control group (without treatment), all animals died. The physicochemical and pharmaceutical properties of the synthesised fluid and the therapeutic results, as seen in the in vivo experiments, provide insights into therapeutic hype...
Journal of Materials Chemistry B, 2017
Magnetic hyperthermia, in which magnetic nanoparticles are introduced into tumors and exposed to an alternating magnetic field (AMF), appears promising since it can lead to increased patients life expectancy. Its efficacy can be further improved by using biocompatible iron oxide magnetosome minerals with better crystallinity and magnetic properties compared with chemically synthesized nanoparticles (IONP-Iron Oxide Nanoparticles). To fabricate such minerals, magnetosomes are first isolated from MSR-1 magnetotactic bacteria, purified to remove potentially toxic organic bacterial residues and stabilized with poly-L-lysine (N-PLL), citric acid (N-CA), oleic acid (N-OA), or carboxymethyl-dextran (N-CMD). The different coated nanoparticles appear to be composed of a cubooctahedral mineral core surrounded by a coating of various thickness, composition, and charge, and to be organized in chains of various lengths. In vitro anti-tumor and heating efficacy of these nanoparticles were examined by bringing them into contact with GL-261 glioblastoma cells and by applying an AMF. This led to a specific absorption rate of 89-196 W/gFe, measured using an AMF of 198 kHz and 34-47 mT, and to a percentage of tumor cell destruction due to nanoparticles exposed to AMF of 10±3 % to 43±3 % depending on the coating agent. It indicated the potential of these nanoparticles for the magnetic hyperthermia tumor treatment.