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Made available in DSpace on 2020-12-12T01:17:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-02 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. Physics Institute Federal University of Goiás Biomagnetism Lab Physics and Biophysics Department São Paulo State University Laboratory of Pharmaceutical Nanotechnology and Drug Delivery Systems School of Pharmacy Federal University of Goiás Biological Sciences Institute Federal University of Goiás Biomagnetism Lab Physics and Biophysics Department São Paulo State University

Made available in DSpace on 2020-12-12T01:46:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-06-01 Cerebral blood flow (CBF) assessment is mainly performed by scintigraphy, computed tomography (CT) and magnetic resonance imaging (MRI). New approaches to assess the CBF through the passage of magnetic nanoparticles (MNPs) to blood-brain barrier (BBB) are convenient to help decrease the use of ionizing radiation and unleash the required MRI schedule in clinics. The development of nanomedicine and new biomedical devices, such as the magnetic particle imaging (MPI), enabled new approaches to study dynamic brain blood flow. In this paper, we employed MNPs and the alternating current biosusceptometry (ACB) to study the brain perfusion. We utilized the mannitol, before the MNPs, injection to modulate the BBB permeability and study its effects on the circulation time of the MNPs in the brain of rats. Also, we characterized a new ACB sensor to increase the systems' applicability to study the MNPs' accumulation, especially in the animals' brain. Our data showed that the injection of mannitol increased the circulation time of MNPs in the brain. Also, the mannitol increased the accumulation of MNPs in the brain. This paper suggests the use of the ACB as a tool to study brain perfusion and accumulation of MNPs in studies of new nano agents focused on the brain diagnostics and treatment. Department of Physics and Biophysics UNESP São Paulo State University Biosciences Institute of Botucatu, Prof. Antonio Celso Wagner Zanin Street Institute of Physics Federal University of Goiás Department of Physics and Biophysics UNESP São Paulo State University Biosciences Institute of Botucatu, Prof. Antonio Celso Wagner Zanin Street

To investigate the role of magnetic anisotropy on magnetic hyperthermia heating efficiency at low field conditions, Mn, MnZn, and MnCo-ferrite nanoparticles were synthesized using the hydrothermal method. The coercive field temperature dependence method was used to determine the blocking temperature distribution of the particles by considering the temperature dependence of anisotropy and magnetization and the random anisotropy axis configuration. The data allowed one to estimate the room-temperature quasi-static superparamagnetic diameter, which was found to be lower than the theoretical value. Magnetic hyperthermia experiments of the magnetic nanocolloids at 522 kHz indicated that soft nanomagnets heat more efficiently at clinically relevant conditions. The heating performance was found to decrease at the higher fraction of blocked nanoparticles. For instance, samples with similar size distribution and mean diameter of 10 nm, at a field amplitude of only 120 Oe (9.6 kA m–1), showed a decrease of specific...

The generation of topological magnetic vortex-domain structures in iron-oxide nanomaterials has promising applications in biomedical scenarios, such as heat generators for hyperthermia treatments. In this report we describe alternative kinds of magnetic-vortex nanoparticles, circular ${\mathrm{Fe}}_{3}{\mathrm{O}}_{4}$ nanodiscs (NDs), and dissect their heating properties by in-depth investigation of their shape and size, stoichiometry, orientations, and switching field ``${H}_{S}$'' behaviors, through experiments and theoretical simulation. We find that the stoichiometric NDs show better heating performance than nonstoichiometric materials because of the significant electron hopping between ${\mathrm{Fe}}^{3+}$ and ${\mathrm{Fe}}^{2+}$ ion. The higher heating efficiency (in terms of specific absorption rate, SAR) is observed only for the higher switching field regime, an effect that is associated with the parallel and perpendicular alignment of nanodiscs with respect to low and high ac magnetic field, respectively. A higher SAR of approximately 270 W/g is observed at a higher switching field (approximately 700 Oe) for NDs of diameter 770 nm, which increases by a factor of 4 at a switching field of approximately 360 Oe for NDs of diameter 200 nm. The reported results suggest that the heating efficiency in these systems can be enhanced by controlling the switching field, which is, in turn, tuned by size, shape, and orientation of circular magnetic vortex nanodiscs.

IR-780 iodide is a fluorescent dye with optical properties in the near-infrared region that has applications in tumor detection and photothermal/photodynamic therapy. This multifunctional effect led to the development of theranostic nanoparticles with both IR-780 and chemotherapeutic drugs such as docetaxel, doxorubicin, and lonidamine. In this work, we developed two albumin-based nanoparticles containing near-infrared IR-780 iodide multifunctional dyes, one of them possessing a magnetic core. Molecular docking with AutoDock Vina studies showed that IR-780 binds to bovine serum albumin (BSA) with greater stability at a higher temperature, allowing the protein binding pocket to better fit this dye. The theoretical analysis corroborates the experimental protocols, where an enhancement of IR-780 was found coupled to BSA at 60 °C, even 30 days after preparation, in comparison to 30 °C. In vitro assays monitoring the viability of Ehrlich ascites carcinoma cells revealed the importance of the inorganic magnetic core on the nanocarrier photothermal-cytotoxic effect. Fluorescence molecular tomography measurements of Ehrlich tumor-bearing Swiss mice revealed the biodistribution of the nanocarriers, with marked accumulation in the tumor tissue (≈3% ID). The histopathological analysis demonstrated strong increase in tumoral necrosis areas after 24 and 72 h after treatment, indicating tumor regression. Tumor regression analysis of nonirradiated animals indicate a IR-780 dose-dependent antitumoral effect with survival rates higher than 70% (animals monitored up to 600 days). Furthermore, an in vivo photothermal therapy procedure was performed and tumor regression was also verified. These results show a novel insight for the biomedical application of IR-780-albumin-based nanocarriers, namely cancer therapy, not only by photoinduced therapy but also by a nonirradiation mechanism. Safety studies (acute oral toxicity, cardiovascular evaluation, and histopathological analysis) suggest potential for clinical translation.

Made available in DSpace on 2020-12-10T19:59:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-02-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Aim: This paper aims to investigate a doxorubicin (DOX) chronic kidney disease rat model using magnetic nanoparticles (MNPs) associated with the alternate current biosusceptometry (ACB) to analyze its different perfusion profiles in both healthy and DOX-injured kidneys. Materials & methods: We used the ACB to detect the MNP kidney perfusion in vivo. Furthermore, we performed biochemical and histological analyses, which sustained results obtained from the ACB system. We also studied the MNP biodistribution. Results: We found that DOX kidney injury alters the MNPs' kidney perfusion. These changes became more intense as the disease progressed. Moreover, DOX has an important effect on MNP biodistribution as the disease evolved. Conclusion: This study provides new applications of MNPs in nephrology, instrumentation, pharmacology, physiology and nanomedicine. Graphical abstract Univ Estadual Paulista, Dept Fis & Biofis, IBB, BR-18618689 Botucatu, SP, Brazil Univ Estadual Paulista, Dept Fisiol, IBB, BR-18618689 Botucatu, SP, Brazil Univ Estadual Paulista, Dept Patol, BR-18618689 Botucatu, SP, Brazil Univ Estadual Paulista, Dept Clin Med, BR-18618689 Botucatu, SP, Brazil Univ Fed Goias, Inst Fis, Alameda Palmeiras St, BR-74690900 Goiania, Go, Brazil Univ Estadual Paulista, Dept Fis & Biofis, IBB, BR-18618689 Botucatu, SP, Brazil Univ Estadual Paulista, Dept Fisiol, IBB, BR-18618689 Botucatu, SP, Brazil Univ Estadual Paulista, Dept Patol, BR-18618689 Botucatu, SP, Brazil Univ Estadual Paulista, Dept Clin Med, BR-18618689 Botucatu, SP, Brazil FAPESP: 2015/14923-9 CAPES: 1491705

The use of central venous catheters (CVC) is highly associated with nosocomial blood infections and its use largely requires a systematic assessment of benefits and risks. Bacterial contamination of these tubes is frequent and may result in development of microbial consortia also known as biofilm. The woven nature of biofilm provides a practical defense against antimicrobial agents, facilitating bacterial dissemination through the patient’s body and development of antimicrobial resistance. In this work, the authors describe the modification of CVC tubing by immobilizing Fe3O4-aminosilane core-shell nanoparticles functionalized with antimicrobial peptide clavanin A (clavA) as an antimicrobial prophylactic towards Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. Its anti-biofilm-attachment characteristic relies in clavA natural activity to disrupt the bacterial lipidic membrane. The aminosilane shell prevents iron leaching, which is an important nutrient for bacterial growth. Fe3O4-clavA-modified CVCs showed to decrease Gram-negative bacteria attachment up to 90% when compared to control clean CVC. Additionally, when hyperthermal treatment is triggered for 5 min at 80 °C in a tubing that already presents bacterial biofilm (CVC-BF), the viability of attached bacteria reduces up to 88%, providing an efficient solution to avoid changing catheter.

Metal-based nanoparticles (NPs) stimulate innate immunity; however, they have never been demonstrated to be capable of aiding the generation of specific cellular immune responses. Therefore, our objective was to evaluate whether iron oxide-based NPs have adjuvant properties in generating cellular Th1, Th17 and TCD8 (Tc1) immune responses. For this purpose, a fusion protein (CMX) composed of Mycobacterium tuberculosis antigens was used as a subunit vaccine. Citrate-coated MnFe(2)O(4) NPs were synthesized by co-precipitation and evaluated by transmission electron microscopy. The vaccine was formulated by homogenizing NPs with the recombinant protein, and protein corona formation was determined by dynamic light scattering and field-emission scanning electron microscopy. The vaccine was evaluated for the best immunization route and strategy using subcutaneous and intranasal routes with 21-day intervals between immunizations. When administered subcutaneously, the vaccine generated specific CD4(+)IFN-γ(+) (Th1) and CD8(+)IFN-γ(+) responses. Intranasal vaccination induced specific Th1, Th17 (CD4(+)IL-17(+)) and Tc1 responses, mainly in the lungs. Finally, a mixed vaccination strategy (2 subcutaneous injections followed by one intranasal vaccination) induced a Th1 (in the spleen and lungs) and splenic Tc1 response but was not capable of inducing a Th17 response in the lungs. This study shows for the first time a subunit vaccine with iron oxide based NPs as an adjuvant that generated cellular immune responses (Th1, Th17 and TCD8), thereby exhibiting good adjuvant qualities. Additionally, the immune response generated by the subcutaneous administration of the vaccine diminished the bacterial load of Mtb challenged animals, showing the potential for further improvement as a vaccine against tuberculosis.

This study reports the successful production of both isometric and anisometric iron oxide-based nanoparticles using, respectively, ammonia and urea for co-precipitating Fe2+/Fe3+ from aqueous solution. Spherical nanoparticles (SNPs) with 10–20 nm in diameter are obtained using ammonia under reflux from 1 h to 9 h, with their relative magnetite/maghemite content decreasing from 10 to 0.05. However, using a lower and higher concentration of urea under reflux from 1 h to 12 h results in rod-like nanoparticles (RNPs) with length/width varying from 40/16 to 80/20 nm and hexagonal nanoparticles (HNPs) with diagonal varying from 150 to 100 nm, respectively. For RNPs (HNPs) the relative magnetite/goethite content increases with refluxing time from 0.25 to 2 (1.25 to 3.75). Hysteresis cycles (300 K) show unblocked SNPs and blocked RNPs and HNPs with coercivity (remanence) increasing with refluxing time from 55 to 80 Oe (1 to 5 emu g−1) and 70 to 130 Oe (5 to 13 emu g−1), respectively. Saturation magnetization of SNPs, RNPs and HNPs spans from 50 to 65 emu g−1, 12 to 60 emu g−1 and 57 to 80 emu g−1, respectively. Under AC magnetic field (522 kHz), with amplitude ranging from 70 to 310 Oe, SNPs show a strong hyperthermia effect, following HNPs with mild and RNPs with weak effects.

Made available in DSpace on 2020-12-12T00:57:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-10-01 We have showed that surface layer can determine cardiac effects of the magnetic nanoparticles (MNPs). Considering the high binding capacity of albumin and low side-effects, the aim of this study was to evaluate the influence of albumin coating on the cardiovascular effects of two manganese ferrite-based MNPs: citrate-coated and bare MNPs. Isolated rat hearts were perfused with citrate-coated magnetic nanoparticles (CiMNPs), citrate albumin-coated magnetic nanoparticles (CiAlbMNPs), bare magnetic nanoparticles (BaMNPs), and albumin-coated magnetic nanoparticles (AlbMNPs). CiMNPs induce a transient decrease in the left ventricular end-systolic pressure, +dP/dt and -dP/dt. These effects were not worsened by albumin coating. BaMNPs significantly increased the left ventricular end-diastolic pressure and perfusion pressure and decreased the +dP/dt and -dP/dt. These effects were completely absent in hearts perfused with AlbMNPs. None of the MNPs changed heart rate or arterial blood pressure in conscious rats. Magnetic signals in isolated hearts perfused with BaMNPs were significantly higher than AlbMNPs perfused hearts. However, the magnetic signal in heart tissue was similar when the MNPs were infused in conscious rats. These data indicate that albumin-coated can reduce cardiovascular effects of MNPs. These findings suggest a protective effect of albumin surface in MNPs, favoring its future therapeutic applications. Department of Physiological Sciences Federal University of Goiás Burnett School of Biomedical Sciences College of Medicine University of Central Florida Physics Institute Federal University of Goiás Department of Physics and Biophysics Biosciences Institute UNESP Department of Physics and Biophysics Biosciences Institute UNESP

Made available in DSpace on 2019-10-06T16:26:57Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-01 In this paper, the application of a technique to evaluate in vivo biodistribution of magnetic nanoparticles (MNP) is addressed: the Multichannel AC Biosusceptometry System (MC-ACB). It allows real-time assessment of magnetic nanoparticles in both bloodstream clearance and liver accumulation, where a complex network of inter-related cells is responsible for MNP uptake. Based on the acquired MC-ACB images, we propose a mathematical model which helps to understand the distribution and accumulation pharmacokinetics of MNP. The MC-ACB showed a high time resolution to detect and monitor MNP, providing sequential images over the particle biodistribution. Utilizing the MC-ACB instrument, we assessed regions corresponding to the heart and liver, and we determined the MNP transfer rates between the bloodstream and the liver. The pharmacokinetic model resulted in having a strong correlation with the experimental data, suggesting that the MC-ACB is a valuable and accessible imaging device to assess in vivo and real-time pharmacokinetic features of MNP. Departamento de Física e Biofísica UNESP/São Paulo State University-Laboratório de Biomagnetismo UNIFAL-MG/Universidade Federal de Alfenas-MG-Departamento de Física ICEx Instituto de Física Universidade Federal de Goiás UNESP/São Paulo State University-Departamento de Bioestatística IBB Departamento de Física e Biofísica UNESP/São Paulo State University-Laboratório de Biomagnetismo UNESP/São Paulo State University-Departamento de Bioestatística IBB

Made available in DSpace on 2019-10-06T15:24:22Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Several applications of nanoparticles rely on the internalization and accumulation of nanocarriers in specific cell compartments and tissues. However, the methods currently employed for characterizing such processes, although well described, are time consuming and do not provide in vivo information, which is a crucial barrier towards translational applications. Here, we hypothesize that the AC Biosusceptometry technique can be employed to assess cell internalization of magnetic nanoparticles, with possible applications in screening assays to track specific biomarkers and cell types. We tested a simpler and easier alternative to study cell internalization and tissue accumulation after perfusion. We utilized citrate coated, manganese ferrite nanoparticles and evaluated the internalization process in mouse macrophages cells (J774.A1) and in an embryonic neural stem cell culture (E14.5) after differentiation in astrocytes and neurons, to assess internalization specificity. Respecting the particles toxicity limits, we tested different concentration of particles, in different incubation times. Sequentially, we imaged the cell cultures to confirm internalization and nanoparticles localization, labeling nucleus and cell body to assure that the particles were inside the cells. Our results showed a linear behavior on internalization for different doses and an optimum incubation time of 2 h. Departamento de Física e Biofísica Institute of Biosciences Sao Paulo State University (Unesp) Center for Neuroregeneration Houston Methodist Research Institute Departamento de Física Faculdade de Física Ciências e Letras de Ribeirão Preto University of Sao Paulo (USP) Instituto de Física Federal University of Goiás Departamento de Física e Biofísica Institute of Biosciences Sao Paulo State University (Unesp) FAPESP: 2015/14914-0 FAPESP: 2017/00842-2

Magnetic nanosorbents are novel materials that have been impacting various applications in environmental fields, including the detection of pollutants and remediation of polluted environments. In this work, the thermal heating effect caused by the interaction of nanoparticles’ magnetic moments with an alternating magnetic field (AMF) – magnetic hyperthermia – is proposed as proof of a concept to illustrate the remote controlled recycling of magnetic nanosorbents during the treatment of water containing toluene, a potentially toxic and volatile contaminant. Nanosorbents were synthesized by functionalization of ∼15 nm coprecipitated cobalt/manganese mixed ferrite with polydimethylsiloxane. Structural, chemical, and magnetic characteristics of the nanosized adsorbent were investigated by elemental analysis (ICP-OES), X-ray diffractometry (XRD), high resolution transmission electron microscopy (HRTEM), Fourier transform infrared spectroscopy (FTIR) and vibrating sample magnetometry (VSM). Batch experiments indicated that nanoadsorbents, which can be magnetically recovered, exhibit high adsorption affinity for toluene in aqueous solution (∼325 mg/g) and that adsorption follows the Langmuir model. Moreover, application of AMF resulted in uniform heating within the nanosorbents (after being magnetically separated from the contaminated water) and triggered toluene desorption/evaporation, leading to accelerated release of pollutants from the nanosorbent, improving its reusability; even after seven cycles the removal efficiency was quite high (83%).

The phenomenon of heat dissipation by magnetic materials interacting with an alternating magnetic field, known as magnetic hyperthermia, is an emergent and promising therapy for many diseases, mainly cancer. Here, a magnetic hyperthermia model for core-shell nanoparticles is developed. The theoretical calculation, different from previous models, highlights the importance of heterogeneity by identifying the role of surface and core spins on nanoparticle heat generation. We found that the most efficient nanoparticles should be obtained by selecting materials to reduce the surface to core damping factor ratio, increasing the interface exchange parameter and tuning the surface to core anisotropy ratio for each material combination. From our results we propose a novel heat-based hyperthermia strategy with the focus on improving the heating efficiency of small sized nanoparticles instead of larger ones. This approach might have important implications for cancer treatment and could help improving clinical efficacy.

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 ± 1.2% and a DL of 17.1 ± 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.

Magnetic nanoparticles dissipate heat when exposed to alternating magnetic fields (AMFs), making them suitable for cancer hyperthermia. Therapeutic heating applications demand accurate characterization of the heating power dissipated by the particles. Specific loss power (SLP) generated by magnetic nanoparticles is estimated from calorimetric heating measurements. Such measurements require adiabatic conditions, yet they are typically performed in an AMF device with non-adiabatic conditions. We have measured heating from four magnetic nanoparticle constructs using a range of frequencies (150–375 kHz) and magnetic fields (4–44 kA/m). We have extended a method developed to estimate SLP from the inherently non-adiabatic measurements, where we identify data ranges that conform to (quasi)-adiabatic conditions. Each time interval of measurement that met a predetermined criterion was used to generate a value of SLP, and the mean from all estimates was selected as the estimated SLP. Despite the application of rigorous selection criteria, measured temperature data displayed variability at specific heating loads resulting in larger variance of calculated mean SLP values. Overall, the results show a linear dependence of the SLP with AMF frequency, as anticipated by current models. Conversely, measured amplitude-dependent SLP profiles of all studied constructs conform to no predictions of current models.

Made available in DSpace on 2018-11-26T15:43:54Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-03-21 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundacao de Amparo a Pesquisa do estado de Goias (FAPEG) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Background: We introduce and demonstrate that the AC biosusceptometry (ACB) technique enables real-time monitoring of magnetic nanoparticles (MNPs) in the bloodstream. We present an ACB system as a simple, portable, versatile, non-invasive, and accessible tool to study pharmacokinetic parameters of MNPs, such as circulation time, in real time. We synthesized and monitored manganese doped iron oxide nanoparticles in the bloodstream of Wistar rats using two different injection protocols. Aiming towards a translational approach, we also simultaneously evaluated cardiovascular parameters, including mean arterial pressure, heart rate, and episodes of arrhythmia in order to secure the well-being of all animals. Results: We found that serial injections increased the circulation time compared with single injections. Immediately after each injection, we observed a transitory drop in arterial pressure, a small drop in heart rate, and no episodes of arrhythmia. Although some cardiovascular effects were observed, they were transitory and easily recovered in both protocols. Conclusions: These results indicate that the ACB system may be a valuable tool for in vivo, real-time MNP monitoring that allows associations with other techniques, such as pulsatile arterial pressure and electrocardiogram recordings, helping ensuring the protocol safety, which is a fundamental step towards clinical applications. Sao Paulo State Univ, Biosci Inst Botucatu, Botucatu, SP, Brazil Univ Fed Goias, Inst Phys, Goiania, Go, Brazil Univ Sao Paulo, Ribeirao Preto Sch Med, Ribeirao Preto, SP, Brazil Univ Fed Goias, Inst Fis, BR-74690900 Goiania, Go, Brazil Sao Paulo State Univ, Biosci Inst Botucatu, Botucatu, SP, Brazil

Non-invasive and real-time monitoring of the heat delivery during magnetic nanoparticle hyperthermia (MNH) is of fundamental importance to predict clinical outcomes for cancer treatment. Infrared thermography (IRT) can determine the surface temperature due to three-dimensional heat delivery inside a subcutaneous tumor, an argument that is supported by numerical simulations. However, for precise temperature determination, it is of crucial relevance to use a correct experimental configuration. This work reports an MNH study using a sarcoma 180 murine tumor containing 3.9 mg of intratumorally injected manganese-ferrite nanoparticles. MNH was performed at low field amplitude and non-uniform field configuration. Five 30 min in vivo magnetic hyperthermia experiments were performed, monitoring the surface temperature with a fiber optical sensor and thermal camera at distinct angles with respect to the animal's surface. The results indicate that temperature errors as large as [Formula: see text]C can occur if the experiment is not properly designed. A new IRT error model is found to explain the data. More importantly, we show how to precisely monitor temperature with IRT during hyperthermia, which could positively impact heat dosimetry and clinical planning.

Modern medicine has been searching for new and more efficient strategies for diagnostics and therapeutics applications. Considering this, porphyrin molecules have received great interest for applications in photodiagnostics and phototherapies, even as magnetic nanoparticles for drug-delivery systems and magnetic-hyperthermia therapy. Aiming to obtain a multifunctional system, which combines diagnostics with therapeutic functions on the same platform, the present study employed UV/vis absorption and fluorescence spectroscopies to evaluate the interaction between meso-tetrakis(p-sulfonatofenyl)porphyrin (TPPS) and maghemite nanoparticles (γ-Fe2O3). These spectroscopic techniques allowed us to describe the dynamics of coupling porphyrins on nanoparticles and estimate the number of 21 porphyrins per nanoparticle. Also, the binding parameters, such as the association constants (Ka = 8.89 × 105 M-1) and bimolecular quenching rate constant (kq = 2.54 × 1014 M-1 s-1) were obtained. These results suggest a static quenching process where the electrostatic attraction plays an essential role. The work shows that spectroscopic techniques are powerful tools to evaluate the coupling of organic molecules and nanoparticles. Besides, the system studied provides a relevant background for potential applications in bionanotechnology and nanomedicine, such as (1) nanodrug delivery system, (2) photodiagnostics/theranostics, and/or (3) a combined action of photodynamic and hyperthermia therapies, working in a synergetic way.

Understanding high-field amplitude electromagnetic heat loss phenomena is of great importance, in particular in the biomedical field, since the heat-delivery treatment plans might rely on analytical models that are only valid at low field amplitudes. Here, we develop a nonlinear response model valid for single- domain nanoparticles of larger particle sizes and higher field amplitudes in comparison to linear response theory. A nonlinear magnetization expression and a generalized heat loss power equation are obtained and compared with the exact solution of the stochastic Landau-Lifshitz-Gilbert equation assuming the giant-spin hypothesis. The model is valid within the hyperthermia therapeutic window and predicts a shift of optimum particle size and distinct heat loss field amplitude exponents. Experimental hyperthermia data with distinct ferrite-based nanoparticles, as well as third harmonic magnetization data supports the nonlinear model, which also has implications for magnetic particle imaging and magnetic thermometry., Comment: 14 pages, 5 figures and 52 references

The dipolar interaction is known to substantially affect the properties of magnetic nanoparticles. This is particularly important when the particles are kept in a fluid suspension or packed within nano-carriers. In addition to its usual long-range nature, in these cases the dipolar interaction may also induce the formation of clusters of particles, thereby strongly modifying their magnetic anisotropies. In this paper we show how AC susceptibility may be used to obtain information regarding the influence of the dipolar interaction in a sample. We develop a model which includes both aspects of the dipolar interaction and may be fitted directly to the susceptibility data. The usual long-range nature of the interaction is implemented using a mean-field approximation, whereas the particle-particle aggregation is modeled using a distribution of anisotropy constants. The model is then applied to two samples studied at different concentrations. One consists of spherical magnetite nanoparticles dispersed in oil and the other of cubic magnetite nanoparticles embedded on polymeric nanospheres. We also introduce a simple technique to address the presence of the dipolar interaction in a given sample, based on the height of the AC susceptibility peaks for different driving frequencies., For their financial support, the authors would like to acknowledge the Brazilian funding agencies FAPESP, CNPq and FAPEG, the funding agencies Spanish MINECO and FEDER, under project MAT2014-53961-R. I. Andreu thanks the Spanish CSIC for her JAE Predoc contract.

Made available in DSpace on 2018-11-26T17:34:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2017-05-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) We describe the development of a joint in vivo/ex vivo protocol to monitor magnetic nanoparticles in animal models. Alternating current biosusceptometry (ACB) enables the assessment of magnetic nanoparticle accumulation, followed by quantitative analysis of concentrations in organs of interest. We present a study of real-time liver accumulation, followed by the assessment of sequential biodistribution using the same technique. For quantification, we validated our results by comparing all of the data with electron spin resonance (ESR). The ACB had viable temporal resolution and accuracy to differentiate temporal parameters of liver accumulation, caused by vasculature extravasation and macrophages action. The biodistribution experiment showed different uptake profiles for different doses and injection protocols. Comparisons with the ESR system indicated a correlation index of 0.993. We present the ACB system as an accessible and versatile tool to monitor magnetic nanoparticles, allowing in vivo and real-time evaluations of distribution and quantitative assessments of particle concentrations. (C) 2017 Elsevier Inc. All rights reserved. Univ Estadual Paulista, Dept Fis & Biofis, Lab Biomagnetismo, IBB, Botucatu, SP, Brazil Univ Fed Goias, Inst Fis, Goiania, Go, Brazil Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77030 USA Univ Estadual Paulista, Fac Med Botucatu, Dept Doencas Trop & Diagnost Imagem, Botucatu, SP, Brazil Univ Sao Paulo, Fac Med Ribeirao Preto, Ribeirao Preto, SP, Brazil Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Fis, Ribeirao Preto, SP, Brazil Univ Estadual Paulista, Dept Fis & Biofis, Lab Biomagnetismo, IBB, Botucatu, SP, Brazil Univ Estadual Paulista, Fac Med Botucatu, Dept Doencas Trop & Diagnost Imagem, Botucatu, SP, Brazil FAPESP: 2010/07639-9 FAPESP: 2011/18696-6 FAPESP: 2013/20842-6 FAPESP: 2015/14914-0

Magnetic nanoparticles (MNPs) are being used in several applications in medicine such as hyperthermia, magnetic particle imaging, in vitro and in vivo bioassay, and still there are many other possibilities for use of these particles to come as research progress in this field. One crucial step of its use is the detection of these particles when present in a certain tissue. For in vitro bioassay, the sample can be harvested and placed inside the detector in optimal conditions to favor sensitivity. However, for in vivo human measurements the system must be noninvasive and conform to the anatomic restrictions requiring sensitive detectors and dedicated setups. In this study, we detect nanoparticles with an AC biosusceptometer having an excitation homogeneous magnetic field with 145 μT, provided by a set of rectangular large Rubens coils driven at 10 Hz. The magnetization induced in the sample was detected by a second-order axial gradiometer (20 mm in diameter and 40 mm of baseline) coupled to an RF Superconducting Quantum Interference Device (SQUID) model 330X (BTi). The MNPs used were manganese ferrite-based surface-coated with citric acid dissolved in water at various concentrations. The colloid is stable at physiological conditions. X-ray diffraction confirmed the spinel structure and using Scherrer's relation revealed a particle size of 17.3 nm. The magnetization curve showed a typical superparamagnetic behavior with a specific saturation magnetization of 51.2 emu g−1. The stock solution of nanoparticles had a concentration of 23.17 mg ml−1, corresponding to 1.7 × 1015 NPs ml−1. Measurements were made in a volume of 30 ml with 20 × 103–100 × 103 dilutions of the stock solution of nanoparticles and performed at distances of 1.1, 1.5 and 2.5 cm from the top of the sample vial to the closest coil of the gradiometer. The limits of detection were 8.1 × 109 NP ml−1, 9.5 × 109 NP ml−1 and 11.0 × 109 NP ml−1 for the distances above. These values suggest that the technique might have interesting applications in the real-time in vivo detection of nanoparticles after systemic injections. The present setup can be improved by using more sensitive SQUID sensors and less noisy cryostats.

In this work we have developed and implement a new approach for the study of magnetoliposomes using Monte Carlo simulations. Our model is based on interaction among nanoparticles considering magnetic dipolar, van der Waals, ionic-steric, and Zeeman interaction potentials. The ionic interaction between nanoparticles and the lipid bilayer is represented by an ionic repulsion electrical surface potential that depends on the nanoparticle-lipid bilayer distance and the concentration of ions in the solution. A direct comparison among transmission electron microscopy, vibrating sample magnetometer, dynamic light scattering, nanoparticle tracking analysis, and experimentally derived static magnetic birefringence and simulation data allow us to validate our implementation. Our simulations suggest that confinement plays an important role in aggregate formation.

Nanostructured magnetic systems have many applications, including potential use in cancer therapy deriving from their ability to heat in alternating magnetic fields. In this work we explore the influence of particle chain formation on the normalized heating properties, or specific loss power (SLP) of both low- (spherical) and high- (parallelepiped) anisotropy ferrite-based magnetic fluids. Analysis of ferromagnetic resonance (FMR) data shows that high particle concentrations correlate with increasing chain length producing decreasing SLP. Monte Carlo simulations corroborate the FMR results. We propose a theoretical model describing dipole interactions valid for the linear response regime to explain the observed trends. This model predicts optimum particle sizes for hyperthermia to about 30% smaller than those previously predicted, depending on the nanoparticle parameters and chain size. Also, optimum chain lengths depended on nanoparticle surface-to-surface distance. Our results might have important implications to cancer treatment and could motivate new strategies to optimize magnetic hyperthermia.