Control of Anisotropy and Magnetic Hyperthermia Effect by Addition of Cobalt on Magnetite Nanoparticles.

Magnetic hyperthermia (MH) has emerged as a promising technology with diverse applications in medical and technological fields, leveraging the remote induction of temperature elevation through an alternating magnetic field. While Fe3O4 nanoparticles with an average size around 12-25 nm are commonly employed in MH systems, this study introduces a strategy to produce smaller particles (less than or equal to 10 nm) with enhanced heating efficiency, as measured by specific power absorption (SPA). We conducted an exhaustive and detailed investigation into the morphological and magnetic properties of CoxFe3-xO4 nanoparticles, aiming to optimize their MH response. By varying the Co content, we successfully tuned the effective magnetic anisotropy while maintaining saturation magnetization nearly constant. The MH analysis indicates that these nanoparticles predominantly heat through the Néel mechanism, demonstrating robust reproducibility across different concentrations, viscosity mediums, and ac field conditions. Notably, we identified an optimal anisotropy or Co concentration that maximizes SPA, crucial for developing magnetic systems requiring particles with specific sizes. This work contributes to advancing the understanding and application of MH, particularly in tailoring nanoparticle properties for targeted and efficient heat generation in various contexts.

Breast Cancer Treatment Using the Magneto-Hyperthermia Technique Associated with Omega-3 Polyunsaturated Fatty Acids' Supplementation and Physical Training.

Breast cancer (BC) presents a growing global concern, mainly for the female population of working age. Their pathophysiology shows challenges when attempting to ensure conventional treatment efficacy without adverse effects. This study aimed to evaluate the efficacy of magneto-hyperthermia (MHT) therapy associated with supplementation with omega-3 polyunsaturated fatty acid (w-3 PUFA) and engagement in physical training (PT) for the triple-negative BC (TNBC) model. First, we assessed the physicochemical properties of iron oxide nanoparticles (ION) in biological conditions, as well as their heating potential for MHT therapy. Then, a bioluminescence (BLI) evaluation of the best tumor growth conditions in the TNBC model (the quantity of implanted cells and time), as well as the efficacy of MHT therapy (5 consecutive days) associated with the previous administration of 8 weeks of w-3 PUFA and PT, was carried out. The results showed the good stability and potential of ION for MHT using 300 Gauss and 420 kHz. In the TNBC model, adequate tumor growth was observed after 14 days of 2 × 106 cells implantation by BLI. There was a delay in tumor growth in animals that received w-3 and PT and a significant decrease associated with MHT. This pioneering combination therapy approach (MHT, omega-3, and exercise) showed a positive effect on TNBC tumor reduction and demonstrated promise for pre-clinical and clinical studies in the future.

Hybrid Magnetic Lipid-Based Nanoparticles for Cancer Therapy.

Cancer is one of the major public health problems worldwide. Despite the advances in cancer therapy, it remains a challenge due to the low specificity of treatment and the development of multidrug resistance mechanisms. To overcome these drawbacks, several drug delivery nanosystems have been investigated, among them, magnetic nanoparticles (MNP), especially superparamagnetic iron oxide nanoparticles (SPION), which have been applied for treating cancer. MNPs have the ability to be guided to the tumor microenvironment through an external applied magnetic field. Furthermore, in the presence of an alternating magnetic field (AMF) this nanocarrier can transform electromagnetic energy in heat (above 42 °C) through Néel and Brown relaxation, which makes it applicable for hyperthermia treatment. However, the low chemical and physical stability of MNPs makes their coating necessary. Thus, lipid-based nanoparticles, especially liposomes, have been used to encapsulate MNPs to improve their stability and enable their use as a cancer treatment. This review addresses the main features that make MNPs applicable for treating cancer and the most recent research in the nanomedicine field using hybrid magnetic lipid-based nanoparticles for this purpose.

Paclitaxel-Loaded Lipid-Coated Magnetic Nanoparticles for Dual Chemo-Magnetic Hyperthermia Therapy of Melanoma.

Melanoma is the most aggressive and metastasis-prone form of skin cancer. Conventional therapies include chemotherapeutic agents, either as small molecules or carried by FDA-approved nanostructures. However, systemic toxicity and side effects still remain as major drawbacks. With the advancement of nanomedicine, new delivery strategies emerge at a regular pace, aiming to overcome these challenges. Stimulus-responsive drug delivery systems might considerably reduce systemic toxicity and side-effects by limiting drug release to the affected area. Herein, we report the development of paclitaxel-loaded lipid-coated manganese ferrite magnetic nanoparticles (PTX-LMNP) as magnetosomes synthetic analogs, envisaging the combined chemo-magnetic hyperthermia treatment of melanoma. PTX-LMNP physicochemical properties were verified, including their shape, size, crystallinity, FTIR spectrum, magnetization profile, and temperature profile under magnetic hyperthermia (MHT). Their diffusion in porcine ear skin (a model for human skin) was investigated after intradermal administration via fluorescence microscopy. Cumulative PTX release kinetics under different temperatures, either preceded or not by MHT, were assessed. Intrinsic cytotoxicity against B16F10 cells was determined via neutral red uptake assay after 48 h of incubation (long-term assay), as well as B16F10 cells viability after 1 h of incubation (short-term assay), followed by MHT. PTX-LMNP-mediated MHT triggers PTX release, allowing its thermal-modulated local delivery to diseased sites, within short timeframes. Moreover, half-maximal PTX inhibitory concentration (IC50) could be significantly reduced relatively to free PTX (142,500×) and Taxol® (340×). Therefore, the dual chemo-MHT therapy mediated by intratumorally injected PTX-LMNP stands out as a promising alternative to efficiently deliver PTX to melanoma cells, consequently reducing systemic side effects commonly associated with conventional chemotherapies.

Hybrid Nanoparticles of Citrate-Coated Manganese Ferrite and Gold Nanorods in Magneto-Optical Imaging and Thermal Therapy.

The development of nanomaterials has drawn considerable attention in nanomedicine to advance cancer diagnosis and treatment over the last decades. Gold nanorods (GNRs) and magnetic nanoparticles (MNPs) have been known as commonly used nanostructures in biomedical applications due to their attractive optical properties and superparamagnetic (SP) behaviors, respectively. In this study, we proposed a simple combination of plasmonic and SP properties into hybrid NPs of citrate-coated manganese ferrite (Ci-MnFe2O4) and cetyltrimethylammonium bromide-coated GNRs (CTAB-GNRs). In this regard, two different samples were prepared: the first was composed of Ci-MnFe2O4 (0.4 wt%), and the second contained hybrid NPs of Ci-MnFe2O4 (0.4 wt%) and CTAB-GNRs (0.04 wt%). Characterization measurements such as UV-Visible spectroscopy and transmission electron microscopy (TEM) revealed electrostatic interactions caused by the opposing surface charges of hybrid NPs, which resulted in the formation of small nanoclusters. The performance of the two samples was investigated using magneto-motive ultrasound imaging (MMUS). The sample containing Ci-MnFe2O4_CTAB-GNRs demonstrated a displacement nearly two-fold greater than just using Ci-MnFe2O4; therefore, enhancing MMUS image contrast. Furthermore, the preliminary potential of these hybrid NPs was also examined in magnetic hyperthermia (MH) and photoacoustic imaging (PAI) modalities. Lastly, these hybrid NPs demonstrated high stability and an absence of aggregation in water and phosphate buffer solution (PBS) medium. Thus, Ci-MnFe2O4_CTAB-GNRs hybrid NPs can be considered as a potential contrast agent in MMUS and PAI and a heat generator in MH.

Engineering Gold Shelled Nanomagnets for Pre-Setting the Operating Temperature for Magnetic Hyperthermia.

This study investigated the fabrication of spherical gold shelled maghemite nanoparticles for use in magnetic hyperthermia (MHT) assays. A maghemite core (14 ± 3 nm) was used to fabricate two samples with different gold thicknesses, which presented gold (g)/maghemite (m) content ratios of 0.0376 and 0.0752. The samples were tested in MHT assays (temperature versus time) with varying frequencies (100-650 kHz) and field amplitudes (9-25 mT). The asymptotic temperatures (T∞) of the aqueous suspensions (40 mg Fe/mL) were found to be in the range of 59-77 °C (naked maghemite), 44-58 °C (g/m=0.0376) and 33-51 °C (g/m=0.0752). The MHT data revealed that T∞ could be successful controlled using the gold thickness and cover the range for cell apoptosis, thereby providing a new strategy for the safe use of MHT in practice. The highest SAR (specific absorption rate) value was achieved (75 kW/kg) using the thinner gold shell layer (334 kHz, 17 mT) and was roughly twenty times bigger than the best SAR value that has been reported for similar structures. Moreover, the time that was required to achieve T∞ could be modeled by changing the thermal conductivity of the shell layer and/or the shape/size of the structure. The MHT assays were pioneeringly modeled using a derived equation that was analytically identical to the Box-Lucas method (which was reported as phenomenological).

Local tumour nanoparticle thermal therapy: A promising immunomodulatory treatment for canine cancer.

Distinct thermal therapies have been used for cancer therapy. For hyperthermia (HT) treatment the tumour tissue is heated to temperatures between 39 and 45°C, while during ablation (AB) temperatures above 50°C are achieved. HT is commonly used in combination with different treatment modalities, such as radiotherapy and chemotherapy, for better clinical outcomes. In contrast, AB is usually used as a single modality for direct tumour cell killing. Both thermal therapies have been shown to result in cytotoxicity as well as immune response stimulation. Immunogenic responses encompass the innate and adaptive immune systems and involve the activation of macrophages, dendritic cells, natural killer cells and T cells. Several heat technologies are used, but great interest arises from nanotechnology-based thermal therapies. Spontaneous tumours in dogs can be a model for cancer immunotherapies with several advantages. In addition, veterinary oncology represents a growing market with an important demand for new therapies. In this review, we will focus on nanoparticle-mediated thermal-induced immunogenic effects, the beneficial potential of integrating thermal nanomedicine with immunotherapies and the results of published works with thermotherapies for cancer using dogs with spontaneous tumours, highlighting the works that evaluated the effect on the immune system in order to show dogs with spontaneous cancer as a good model for evaluated the immunomodulatory effect of nanoparticle-mediated thermal therapies.

Superparamagnetic and highly bioactive SPIONS/bioactive glass nanocomposite and its potential application in magnetic hyperthermia.

Magnetic bioactive glass-ceramics are biomaterials applied for magnetic hyperthermia in bone cancer treatment, thereby treating the bone tumor besides regenerating the damaged bone. However, combining high bioactivity and high saturation magnetization remains a challenge since the thermal treatment step employed to grow magnetic phases is also related to loss of bioactivity. Here, we propose a new nanocomposite made of superparamagnetic iron oxide nanoparticles (SPIONs) dispersed in a sol-gel-derived bioactive glass matrix, which does not need any thermal treatment for crystallization of magnetic phases. The scanning and transmission electron microscopies, X-ray diffraction, and dynamic light scattering results confirm that the SPIONs are actually embedded in a nanosized glass matrix, thus forming a nanocomposite. Magnetic and calorimetric characterizations evidence their proper behavior for hyperthermia applications, besides evidencing inter-magnetic nanoparticle interactions within the nanocomposite. Bioactivity and in vitro characterizations show that such nanocomposites exhibit apatite-forming properties similar to the highly bioactive parent glass, besides being osteoinductive. This methodology is a new alternative to produce magnetic bioactive materials to which the magnetic properties only rely on the quality of the SPIONs used in the synthesis. Thereby, these nanocomposites can be recognized as a new class of bioactive materials for applications in bone cancer treatment by hyperthermia.

Folate-Targeted PEGylated Magnetoliposomes for Hyperthermia-Mediated Controlled Release of Doxorubicin.

Doxorubicin (DOX) is a chemotherapeutic agent commonly used for the treatment of solid tumors. However, the cardiotoxicity associated with its prolonged use prevents further adherence and therapeutic efficacy. By encapsulating DOX within a PEGylated liposome, Doxil® considerably decreased DOX cardiotoxicity. By using thermally sensitive lysolipids in its bilayer composition, ThermoDox® implemented a heat-induced controlled release of DOX. However, both ThermoDox® and Doxil® rely on their passive retention in tumors, depending on their half-lives in blood. Moreover, ThermoDox® ordinarily depend on invasive radiofrequency-generating metallic probes for local heating. In this study, we prepare, characterize, and evaluate the antitumoral capabilities of DOX-loaded folate-targeted PEGylated magnetoliposomes (DFPML). Unlike ThermoDox®, DOX delivery via DFPML is mediated by the heat released through dynamic hysteresis losses from magnetothermal converting systems composed by MnFe2O4 nanoparticles (NPs) under AC magnetic field excitation-a non-invasive technique designated magnetic hyperthermia (MHT). Moreover, DFPML dismisses the use of thermally sensitive lysolipids, allowing the use of simpler and cheaper alternative lipids. MnFe2O4 NPs and DFPML are fully characterized in terms of their size, morphology, polydispersion, magnetic, and magnetothermal properties. About 50% of the DOX load is released from DFPML after 30 min under MHT conditions. Being folate-targeted, in vitro DFPML antitumoral activity is higher (IC50 ≈ 1 µg/ml) for folate receptor-overexpressing B16F10 murine melanoma cells, compared to MCF7 human breast adenocarcinoma cells (IC50 ≈ 4 µg/ml). Taken together, our results indicate that DFPML are strong candidates for folate-targeted anticancer therapies based on DOX controlled release.

Synthesis and Characterization of Magnetic Composite Theragnostics by Nano Spray Drying.

Composites of magnetite nanoparticles encapsulated with polymers attract interest for many applications, especially as theragnostic agents for magnetic hyperthermia, drug delivery, and magnetic resonance imaging. In this work, magnetite nanoparticles were synthesized by coprecipitation and encapsulated with different polymers (Eudragit S100, Pluronic F68, Maltodextrin, and surfactants) by nano spray drying technique, which can produce powders of nanoparticles from solutions or suspensions. Transmission and scanning electron microscopy images showed that the bare magnetite nanoparticles have 10.5 nm, and after encapsulation, the particles have approximately 1 µm, with size and shape depending on the material's composition. The values of magnetic saturation by SQUID magnetometry and mass residues by thermogravimetric analysis were used to characterize the magnetic content in the materials, related to their magnetite/polymer ratios. Zero-field-cooling and field-cooling (ZFC/FC) measurements showed how blocking temperatures of the powders of the composites are lower than that of bare magnetite, possibly due to lower magnetic coupling, being an interesting system to study magnetic interactions of nanoparticles. Furthermore, studies of cytotoxic effect, hydrodynamic size, and heating capacity for hyperthermia (according to the application of an alternate magnetic field) show that these composites could be applied as a theragnostic material for a non-invasive administration such as nasal.

Combination of selol nanocapsules and magnetic hyperthermia hinders breast tumor growth in aged mice after a short-time treatment.

Short time treatment with reduced dosages of selol-loaded PLGA nanocapsules (NcSel) combined with magnetic hyperthermia (MHT) is evaluated in aged Erhlich tumor-bearing mice. Clinical, hematological, biochemical, genotoxic and histopathological parameters are assessed during 7 d treatment with NcSel and MHT, separately or combined. The time evolution of the tumor volume is successfully modeled using the logistic mathematical model. The combined therapy comprising NcSel and MHT is able to hinder primary tumor growth and a case of complete tumor remission is recorded. Moreover, no metastasis was diagnosed and the adverse effects are negligible. NcSel plus MHT may represent an effective and safe alternative to cancer control in aged patients. Future clinical trials are encouraged.

Understanding the Dependence of Nanoparticles Magnetothermal Properties on Their Size for Hyperthermia Applications: A Case Study for La-Sr Manganites.

Magnetic oxides are promising materials for alternative health diagnoses and treatments. The aim of this work is to understand the dependence of the heating power with the nanoparticle (NP) mean size, for the manganite composition La0.75Sr0.25MnO3 (LSMO)-the one with maximum critical temperature for the whole La/Sr ratio of the series. We have prepared four different samples, each one annealed at different temperatures, in order to produce different mean NP sizes, ranging from 26 nm up to 106 nm. Magnetization measurements revealed a FC-ZFC irreversibility and from the coercive field as function of temperature we determined the blocking temperature. A phase diagram was delivered as a function of the NP mean size and, based on this, the heating mechanism understood. Small NPs (26 nm) is heated up within the paramagnetic range of temperature (T>Tc), and therefore provide low heating efficiency; while bigger NPs are heated up, from room temperature, within the magnetically blocked range of temperature (TT>TB), for intermediate mean diameter size of 37 nm, with maximum efficiency of heat transfer.

Calcium Phosphate-Based Bioceramics in the Treatment of Osteosarcoma: Drug Delivery Composites and Magnetic Hyperthermia Agents.

The use of biomaterials in medicine is not recent, and in the last few decades, the research and development of biocompatible materials had emerged. Hydroxyapatite (HAp), a calcium phosphate that constitutes a large part of the inorganic composition of human bones and teeth, has been used as an interesting bioceramic material. Among its applications, HAp has been used to carry antitumor drugs, such as doxorubicin, cisplatin, and gemcitabine. Such HAp-based composites have an essential role in anticancer drug delivery systems, including the treatment of osteosarcoma. In addition, the association of this bioceramic with magnetic nanoparticles (MNPs) has also been used as an effective agent of local magnetic hyperthermia. Further, the combined approach of the aforementioned techniques (HAp scaffolds combined with anti-tumor drugs and MNPs) is also an attractive therapeutical alternative. Considering the promising role of the use of bioceramics in modern medicine, we proposed this review, presenting an updated perspective on the use of HAp in the treatment of cancer, especially osteosarcoma. Finally, after giving the current progress in this field, we highlight the urgent need for efforts to provide a better understanding of their potential applications.

Therapeutic Efficiency of Multiple Applications of Magnetic Hyperthermia Technique in Glioblastoma Using Aminosilane Coated Iron Oxide Nanoparticles: In Vitro and In Vivo Study.

Magnetic hyperthermia (MHT) has been shown as a promising alternative therapy for glioblastoma (GBM) treatment. This study consists of three parts: The first part evaluates the heating potential of aminosilane-coated superparamagnetic iron oxide nanoparticles (SPIONa). The second and third parts comprise the evaluation of MHT multiple applications in GBM model, either in vitro or in vivo. The obtained heating curves of SPIONa (100 nm, +20 mV) and their specific absorption rates (SAR) stablished the best therapeutic conditions for frequencies (309 kHz and 557 kHz) and magnetic field (300 Gauss), which were stablished based on three in vitro MHT application in C6 GBM cell line. The bioluminescence (BLI) signal decayed in all applications and parameters tested and 309 kHz with 300 Gauss have shown to provide the best therapeutic effect. These parameters were also established for three MHT applications in vivo, in which the decay of BLI signal correlates with reduced tumor and also with decreased tumor glucose uptake assessed by positron emission tomography (PET) images. The behavior assessment showed a slight improvement after each MHT therapy, but after three applications the motor function displayed a relevant and progressive improvement until the latest evaluation. Thus, MHT multiple applications allowed an almost total regression of the GBM tumor in vivo. However, futher evaluations after the therapy acute phase are necessary to follow the evolution or tumor total regression. BLI, positron emission tomography (PET), and spontaneous locomotion evaluation techniques were effective in longitudinally monitoring the therapeutic effects of the MHT technique.

Predictive Model for Delivery Efficiency: Erythrocyte Membrane-Camouflaged Magnetofluorescent Nanocarriers Study.

Delivery efficiencies of theranostic nanoparticles (NPs) based on passive tumor targeting strongly depend either on their blood circulation time or on appropriate modulations of the tumor microenvironment. Therefore, predicting the NP delivery efficiency before and after a tumor microenvironment modulation is highly desirable. Here, we present a new erythrocyte membrane-camouflaged magnetofluorescent nanocarrier (MMFn) with long blood circulation time (92 h) and high delivery efficiency (10% ID for Ehrlich murine tumor model). MMFns owe their magnetic and fluorescent properties to the incorporation of manganese ferrite nanoparticles (MnFe2O4 NPs) and IR-780 (a lipophilic indocyanine fluorescent dye), respectively, to their erythrocyte membrane-derived camouflage. MMFn composition, morphology, and size, as well as optical absorption, zeta potential, and fluorescent, magnetic, and magnetothermal properties, are thoroughly examined in vitro. We then present an analytical pharmacokinetic (PK) model capable of predicting the delivery efficiency (DE) and the time of peak tumor uptake (tmax), as well as changes in DE and tmax due to modulations of the tumor microenvironment, for potentially any nanocarrier. Experimental PK data sets (blood and tumor amounts of MMFns) are simultaneously fit to the model equations using the PK modeling software Monolix. We then validate our model analytical solutions with the numerical solutions provided by Monolix. We also demonstrate how our a priori nonmechanistic model for passive targeting relates to a previously reported mechanistic model for active targeting. All in vivo PK studies, as well as in vivo and ex vivo biodistribution studies, were conducted using two noninvasive techniques, namely, fluorescence molecular tomography (FMT) and alternating current biosusceptometry (ACB). Finally, histopathology corroborates our PK and biodistribution results.

Magnetic Hybrid Wax Nanocomposites as Externally Controlled Theranostic Vehicles: High MRI Enhancement and Synergistic Magnetically Assisted Thermo/Chemo Therapy.

To fight against cancer, smarter drugs and drug delivery systems are required both to boost the efficiency of current treatments while reducing deleterious side effects, and combine diagnosis/monitoring with therapy (theranosis) in the search for the final goal of personalized medicine. This work presents the design, preparation, and proof-of-principle validation of a novel hybrid organic-inorganic nanocomposite joining together non-invasive imaging capabilities through magnetic resonance imaging and externally actuated therapeutic properties through a combination of chemo- and thermotherapy. The lipidic matrix of the nanocomposite was composed of carnauba wax, which was simultaneously dual loaded with magnetite nanoparticles and the anticancer drug Oncocalyxone A. Obtained formulations were fully characterized and showed outstanding performances as T2 -contrast agents in magnetic resonance imaging (r2 >800 mm-1 s-1 ), heat generating sources in magnetic hyperthermia (specific absorption rate, SAR>200 W g-1 Fe ), and magnetically responsive drug delivery vehicles. The potential of the designed formulations as theranostic agents was validated in vitro and results indicated a synergistic thermo/chemotherapeutic effect derived from heat generation and controlled drug delivery to cancer growth. Thereby, this external control over the drug delivery profile and the integrated imaging capability open the door to personalized cancer medicine and real-time monitoring of tumor progression.

Therapeutic potential of low-cost nanocarriers produced by green synthesis: macrophage uptake of superparamagnetic iron oxide nanoparticles.

Aim: The primary goal of this work was to synthesize low-cost superparamagnetic iron oxide nanoparticles (SPIONs) with the aid of coconut water and evaluate the ability of macrophages to internalize them. Our motivation was to determine potential therapeutic applications in drug-delivery systems associated with magnetic hyperthermia. Materials & methods: We used the following characterization techniques: x-ray and electron diffractions, electron microscopy, spectrometry and magnetometry. Results: The synthesized SPIONs, roughly 4 nm in diameter, were internalized by macrophages, likely via endocytic/phagocytic pathways. They were randomly distributed throughout the cytoplasm and mainly located in membrane-bound compartments. Conclusion: Nanoparticles presented an elevated intrinsic loss power value and were not cytotoxic to mammalian cells. Thus, we suggest that low-cost SPIONs have great therapeutic potential.

Therapeutic evaluation of magnetic hyperthermia using Fe3O4-aminosilane-coated iron oxide nanoparticles in glioblastoma animal model / Avaliação terapêutica da técnica de magneto-hipertermia utilizando nanopartículas de Fe3O4 recobertas com aminosilana em modelo animal de glioblastoma

ABSTRACT Objective: To evaluate the potential of magnetic hyperthermia using aminosilane-coated superparamagnetic iron oxide nanoparticles in glioblastoma tumor model. Methods: The aminosilane-coated superparamagnetic iron oxide nanoparticles were analyzed as to their stability in aqueous medium and their heating potential through specific absorption rate, when submitted to magnetic hyperthermia with different frequencies and intensities of alternating magnetic field. In magnetic hyperthermia in vitro assays, the C6 cells cultured and transduced with luciferase were analyzed by bioluminescence in the absence/presence of alternating magnetic field, and also with and without aminosilane-coated superparamagnetic iron oxide nanoparticles. In the in vivo study, the measurement of bioluminescence was performed 21 days after glioblastoma induction with C6 cells in rats. After 24 hours, the aminosilane-coated superparamagnetic iron oxide nanoparticles were implanted in animals, and magnetic hyperthermia was performed for 40 minutes, using the best conditions of frequency and intensity of alternating magnetic field tested in the in vitro study (the highest specific absorption rate value) and verified the difference of bioluminescence before and after magnetic hyperthermia. Results: The aminosilane-coated superparamagnetic iron oxide nanoparticles were stable, and their heating capacity increased along with higher frequency and intensity of alternating magnetic field. The magnetic hyperthermia application with 874kHz and 200 Gauss of alternating magnetic field determined the best value of specific absorption rate (194.917W/g). When these magnetic hyperthermia parameters were used in in vitro and in vivo analysis, resulted in cell death of 52.0% and 32.8%, respectively, detected by bioluminescence. Conclusion: The magnetic hyperthermia was promissing for the therapeutical process of glioblastoma tumors in animal model, using aminosilane-coated superparamagnetic iron oxide nanoparticles, which presented high specific absorption rate.

RESUMO Objetivo: Avaliar o potencial da técnica de magneto-hipertermia utilizando nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana em modelo de tumores de glioblastoma. Métodos: As nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana foram avaliadas quanto à sua estabilidade em meio aquoso e a seu potencial de aquecimento pela taxa de absorção específica, quando submetidas à magneto-hipertermia, com diferentes frequências e intensidades de campo magnético alternado. Nos ensaios de magneto-hipertermia in vitro, as células C6 cultivadas e transduzidas com luciferase foram avaliadas por bioluminescência na presença/ausência do campo magnético alternado, como também com e sem nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana. No estudo in vivo, a medida de bioluminescência foi adquirida no 21º dia após indução do glioblastoma com células C6 nos ratos. Após 24 horas, as nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana foram implantadas no animal, tendo sido realizada a magneto-hipertermia por 40 minutos, nas melhores condições de frequência e intensidade de campo magnético alternado testado no estudo in vitro (maior valor da taxa de absorção específica); foi verificada a diferença do bioluminescência antes e após a magneto-hipertermia. Resultados: As nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana se mostraram estáveis, e sua capacidade de aquecimento aumentou com o incremento da frequência e da intensidade de campo magnético alternado. A aplicação da magneto-hipertermia, com 874kHz e 200 Gauss do campo magnético alternado, determinou o melhor valor da taxa de absorção específica (194,917W/g). Quando utilizados, estes parâmetros de magneto-hipertermia in vitro resultaram em morte celular de 52,0% e in vivo de 32,8% por bioluminescência. Conclusão: A técnica de magneto-hipertermia foi promissora para o processo terapêutico de tumores de glioblastoma no modelo animal utilizando as nanopartículas superparamagnéticas de óxido de ferro recobertas com aminosilana recobertas com aminosilana, que apresentaram alta taxa de absorção específica.

Triggered release of paclitaxel from magnetic solid lipid nanoparticles by magnetic hyperthermia.

We developed a magnetic solid lipid nanoparticles formulation of paclitaxel (PTX-loaded MSLNs) via emulsification-diffusion method. The physicochemical characterization of PTX-loaded MSLNs was performed by AFM, DLS, determination of entrapment efficiency (EE) and drug loading (DL), DSC, VSM, and physical stability. The in vitro effect of temperature and pulsed magnetic hyperthermia on drug release were studied. PTX-loaded MSLNs had a particle diameter around 250 nm with a narrow size distribution, spherical morphology, EE of 67.3 ±â€¯1.2% and a DL of 17.1 ±â€¯0.4 µg/mg. A decrease of the melting point of the lipid was observed following the preparation of the MSLNs. A threefold increase in the in vitro drug release rate was seen when temperature was raised from 25 to 43 °C. The lipid coating of MPs confer a temperature-dependent drug release and magnetic hyperthermia was used to trigger controlled PTX release from MSLNs.

Sub-Micrometer Magnetic Nanocomposites: Insights into the Effect of Magnetic Nanoparticles Interactions on the Optimization of SAR and MRI Performance.

There is increasing interest in the development of new magnetic polymeric carriers for biomedical applications such as trigger-controlled drug release, magnetic hyperthermia (MH) for the treatment of cancer, and as contrast agents in magnetic resonance imaging (MRI). This work describes the synthesis of sub-micrometer and magnetic polymer nanocomposite capsules (MPNCs) by combining in one single platform the biodegradable polymer poly-ε-caprolactone (PCL) and different concentrations of ∼8 nm oleic acid (OA)-functionalized magnetite nanoparticles (Fe3O4@OA), employing the oil-in-water emulsion/solvent evaporation method. The MPNCs showed a significant increase in particle size from ∼400 to ∼800 nm as the magnetic loading in the organic-inorganic hybrids increases from 1.0% to 10%. The MPNCs presented high incorporation efficiency of Fe3O4@OA nanoparticles, good colloidal stability, and super-paramagnetic properties. Interestingly, electron microscopy results showed that the Fe3O4@OA nanoparticles were preferentially located at the surface of the capsules. Evaluation of the magnetic properties showed that the saturation magnetization and the blocking temperature of the MPNCs samples increased as a function of the Fe3O4@OA loading. All the MPNCs exhibited heating when subjected to MH, and showed good specific absorption rates. Use of the formulations decreased the longitudinal (T1) and transverse (T2) relaxation times of water protons' nuclei, with excellent transverse relaxivity (r2) values, especially in the case of the formulation with lowest Fe3O4@OA loading. Furthermore, the MPNCs-cell interaction was studied, and MPNCs showed lower cellular toxicity to normal cells compared to cancer cells. These findings help in understanding the relationships between magnetic nanoparticles and polymeric capsules, opening perspectives for their potential clinical uses as simultaneous heating sources and imaging probes in MH and MRI, respectively.