The dipolar interaction is known to substantially affect the properties of magnetic nanoparticles... more 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 inside nanocarriers. 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 important 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 solution, 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 PLGA nanospheres. We also introduce a simple technique to access the importance of the dipolar interaction in a given sample, based on the height of the AC susceptibility peaks for different driving frequencies. Our results help illustrate the important effect that the dipolar interaction has in most nanoparticle samples.
The magnetic response of nanostructures plays an important role on biomedical applications being ... more The magnetic response of nanostructures plays an important role on biomedical applications being strongly influenced by the magnetic anisotropy. In this work we investigate the role of temperature, particle concentration and nanoparticle arrangement forming aggregates in the effective magnetic anisotropy of Mn-Zn ferrite-based nanoparticles. Electron magnetic resonance and coercivity temperature dependence analyses, were critically compared for the estimation of the anisotropy. We found that the temperature dependence of the anisotropy follows the Callen-Callen model, while the symmetry depends on the particle concentration. At low concentration one observes only an uniaxial term, while increasing a cubic contribution has to be added. The effective anisotropy was found to increase the higher the particle concentration on magnetic colloids, as long as the easy axis was at the same direction of the nanoparticle chain. Increasing even further the concentration up to a highly packed condition (powder sample) one observes a decrease of the anisotropy, that was attributed to the random anisotropy axes configuration.
Backgorund: Non-invasive magnetic imaging techniques are necessary to assist assist magnetic nano... more Backgorund: Non-invasive magnetic imaging techniques are necessary to assist assist magnetic nanoparticles biomedical applications, mainly detecting their distribution inside the body. In Alternating Current Biosusceptometry (ACB), the magnetic nanoparticles magnetization response under an oscillating magnetic eld, which is applied through an excitation coil, is detected with a balanced detection coil system. Results: We built a Multi-Channel ACB system (MC-ACB) containing nineteen pick-up coils and obtained 2D quantitative images of magnetic nanoparticles distributions by solving an inverse problem. We reconstructed the magnetic nanoparticles spatial distributions in a eld of view of 14×14 cm² with a spatial resolution of 2.0 cm and sensitivity in the milligram scale. A correlation coe cient between quantitative reconstructed and nominal magnetic nanoparticles distributions above 0.6 was found for all measurements. Conclusion: Besides other interesting features such as su cient large eld of view dimension for mice and rat studies, portability, and the ability to assess the quantitative magnetic nanoparticles distributions in real-time, the MC-ACB system is a promising tool for quantitative imaging of magnetic nanoparticles distributions in real-time, offering an affordable setup for easy access in clinical or laboratory environments.
Inducing immunogenic cell death (ICD) during cancer therapy is a major challenge that might signi... more Inducing immunogenic cell death (ICD) during cancer therapy is a major challenge that might significantly improve patient survival. The purpose of this study was to develop a theranostic nanocarrier, capable both of conveying a cytotoxic thermal dose when mediating photothermal therapy (PTT) after its intravenous delivery, and of consequently inducing ICD, improving survival. The nanocarrier consists of red blood cell membranes (RBCm) embedding the near-infrared dye IR-780 (IR) and camouflaging Mn-ferrite nanoparticles (RBCm-IR-Mn). The RBCm-IR-Mn nanocarriers were characterized by size, morphology, surface charge, magnetic, photophysical, and photothermal properties. Their photothermal conversion efficiency was found to be size- and concentration-dependent. Late apoptosis was observed as the cell death mechanism for PTT. Calreticulin and HMGB1 protein levels increased for in vitro PTT with temperature around 55 °C (ablative regime) but not for 44 °C (hyperthermia), suggesting ICD e...
Biomimetic nanoparticles hold great promise for photonic-mediated nanomedicine due to the associa... more Biomimetic nanoparticles hold great promise for photonic-mediated nanomedicine due to the association of the biological functionality of the membrane with the physical/chemical goals of organic/inorganic structures, but studies involving fluorescent biomimetic vesicles are still scarce. The purpose of this article is to determine how photothermal therapy (PTT) with theranostic IR-780-based nanoparticles depends on the dye content, cholesterol content, lipid bilayer phase and cell membrane type. The photophysical responses of synthetic liposomes, cell membrane vesicles and hybrid nanoparticles are compared. The samples were characterized by nanoparticle tracking analysis, photoluminescence, electron spin resonance, and photothermal- and heat-mediated drug release experiments, among other techniques. The photothermal conversion efficiency (PCE) was determined using Roper’s method. All samples excited at 804 nm showed three fluorescence bands, two of them independent of the IR-780 cont...
Since magnetic nanoparticles (MNPs) have been used as multifunctional probes to diagnose and trea... more Since magnetic nanoparticles (MNPs) have been used as multifunctional probes to diagnose and treat liver diseases in recent years, this study aimed to assess how the condition of cirrhosis-associated hepatocarcinogenesis alters the biodistribution of hepatic MNPs. Using a real-time image acquisition approach, the distribution profile of MNPs after intravenous administration was monitored using an AC biosusceptometry (ACB) assay. We assessed the biodistribution profile based on the ACB images obtained through selected regions of interest (ROIs) in the heart and liver position according to the anatomical references previously selected. The signals obtained allowed for the quantification of pharmacokinetic parameters, indicating that the uptake of hepatic MNPs is compromised during liver cirrhosis, since scar tissue reduces blood flow through the liver and slows its processing function. Since liver monocytes/macrophages remained constant during the cirrhotic stage, the increased intrah...
This study investigated the fabrication of spherical gold shelled maghemite nanoparticles for use... more 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 bes...
Doxorubicin (DOX) is a chemotherapeutic agent commonly used for the treatment of solid tumors. Ho... more 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 nanopa...
Once administered in an organism, the physiological parameters of magnetic nanoparticles (MNPs) m... more Once administered in an organism, the physiological parameters of magnetic nanoparticles (MNPs) must be addressed, as well as their possible interactions and retention and elimination profiles. Alternating current biosusceptometry (ACB) is a biomagnetic detection system used to detect and quantify MNPs. The aims of this study were to evaluate the biodistribution and clearance of MNPs profiles through long-time in vivo analysis and determine the elimination time carried out by the association between the ACB system and MnFe2O4 nanoparticles. The liver, lung, spleen, kidneys, and heart and a blood sample were collected for biodistribution analysis and, for elimination analysis, and over 60 days. During the period analyzed, the animal’s feces were also collectedd. It was possible to notice a higher uptake by the liver and the spleen due to their characteristics of retention and uptake. In 60 days, we observed an absence of MNPs in the spleen and a significant decay in the liver. We als...
The generation of topological magnetic vortex-domain structures in iron-oxide nanomaterials has p... more 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 Fe 3 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 Fe 3+ and 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.
The use of magnetic nanoparticles (MNPs) in biomedical applications requires the quantitative kno... more The use of magnetic nanoparticles (MNPs) in biomedical applications requires the quantitative knowledge of their quantitative distribution within the body. AC Biosusceptometry (ACB) is a biomagnetic technique recently employed to detect MNPs in vivo by measuring the MNPs response when exposed to an alternate magnetic field. The ACB technique presents some interesting characteristics: non-invasiveness, low operational cost, high portability, and no need for magnetic shielding. ACB conventional methods until now provided only qualitative information about the MNPs’ mapping in small animals. We present a theoretical model and experimentally demonstrate the feasibility of ACB reconstructing 2D quantitative images of MNPs’ distributions. We employed an ACB single-channel scanning approach, measuring at 361 sensor positions, to reconstruct MNPs’ spatial distributions. For this, we established a discrete forward problem and solved the ACB system’s inverse problem. Thus, we were able to det...
Purpose: Noninvasive thermometry during magnetic nanoparticle hyperthermia (MNH) remains a challe... more Purpose: Noninvasive thermometry during magnetic nanoparticle hyperthermia (MNH) remains a challenge. Our pilot study proposes a methodology to determine the noninvasive intratumoral thermal dose during MNH in the subcutaneous tumor model. Methods: Two groups of Ehrlich bearing-mice with solid and subcutaneous carcinoma, a control group (n ¼ 6), and a MNH treated group (n ¼ 4) were investigated. Histopathology was used to evaluate the percentage of non-viable lesions in the tumor. MNH was performed at 301 kHz and 17.5 kA.m À1 , using a multifunctional nanocarrier. Surface temperature measurements were obtained using an infrared camera, where an ROI with 750 pixels was used for comparison with computer simulations. Realistic simulations of the bioheat equation were obtained by combining histopathology intratumoral lesion information and surface temperature agreement of at least 50% of the pixel's temperature data calculated and measured at the surface. Results: One animal of the MNH group showed tumor recurrence, while two others showed complete tumor remission (monitored for 585 days). Sensitivity analysis of the simulation parameters indicated low tumor blood perfusion. Numerical simulations indicated, for the animals with complete remission, an irreversible tissue injury of 91 ± 5% and 100%, while the one with recurrence had a lower value, 56 ± 7%. The computer simulations also revealed the in vivo heat efficiency of the nanocarrier. Conclusion: A new methodology for determining noninvasively the three-dimensional intratumoral thermal dose during MNH was developed. The method demonstrates the potential for predicting the long-term preclinical outcome of animals treated with MNH.
Isometric and anisometric iron oxide magnetic nanoparticles, synthesized via an eco-friendly rout... more Isometric and anisometric iron oxide magnetic nanoparticles, synthesized via an eco-friendly route, present modulated heating efficiency for magnetic hyperthermia applications.
The study demonstrates the performance of heating efficiency in single‐phase and binary phase spi... more The study demonstrates the performance of heating efficiency in single‐phase and binary phase spinel ferrite nanosystems. Ferrimagnetic cobalt ferrite (CoFe2O4) (CFO) and superparamagnetic copper ferrite/copper oxide (CuFe2O4/CuO) (CuF) nanosystems of different particle sizes were synthesized through a microwave‐assisted coprecipitation method. The heating behavior was observed in range of both field amplitudes (8‐24 kA/m at 516 kHz) and frequencies (325‐973 kHz at 12 kA/m). The heating efficiency was analyzed and compared by means of particle size, magnetization, effective anisotropy constant, and Néel relaxation mechanism. Indeed, the heating rate was maximized in larger ferrite particles with low effective anisotropy constant. Moreover, though the magnetization and effective anisotropy constant of single‐phase CoFe2O4 nanoparticles were higher, the binary phase CuFe2O4/CuO nanosystems of similar crystallite size (28 nm) exhibited superior heating efficiency (4.21°C/s). For a fiel...
The magnetic response of nanostructures plays an important role on biomedical applications being ... more The magnetic response of nanostructures plays an important role on biomedical applications being strongly influenced by the magnetic anisotropy. In this work we investigate the role of temperature, particle concentration and nanoparticle arrangement forming aggregates in the effective magnetic anisotropy of Mn-Zn ferrite-based nanoparticles. Electron magnetic resonance and coercivity temperature dependence analyses, were critically compared for the estimation of the anisotropy. We found that the temperature dependence of the anisotropy follows the Callen-Callen model, while the symmetry depends on the particle concentration. At low concentration one observes only an uniaxial term, while increasing a cubic contribution has to be added. The effective anisotropy was found to increase the higher the particle concentration on magnetic colloids, as long as the easy axis was at the same direction of the nanoparticle chain. Increasing even further the concentration up to a highly packed condition (powder sample) one observes a decrease of the anisotropy, that was attributed to the random anisotropy axes configuration.
Understanding high-field amplitude electromagnetic heat loss phenomena is of great importance, in... more Understanding high-field amplitude electromagnetic heat loss phenomena is of great importance, in particular, in the biomedical field, because 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 the 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, which is often obtained experimentally using a phenomenological allometric function. Experimental hyperthermia data with distinct ferrite-based nanoparticles and third harmonic magnetizati...
The dipolar interaction is known to substantially affect the properties of magnetic nanoparticles... more 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 inside nanocarriers. 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 important 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 solution, 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 PLGA nanospheres. We also introduce a simple technique to access the importance of the dipolar interaction in a given sample, based on the height of the AC susceptibility peaks for different driving frequencies. Our results help illustrate the important effect that the dipolar interaction has in most nanoparticle samples.
The dipolar interaction is known to substantially affect the properties of magnetic nanoparticles... more 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 inside nanocarriers. 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 important 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 solution, 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 PLGA nanospheres. We also introduce a simple technique to access the importance of the dipolar interaction in a given sample, based on the height of the AC susceptibility peaks for different driving frequencies. Our results help illustrate the important effect that the dipolar interaction has in most nanoparticle samples.
The magnetic response of nanostructures plays an important role on biomedical applications being ... more The magnetic response of nanostructures plays an important role on biomedical applications being strongly influenced by the magnetic anisotropy. In this work we investigate the role of temperature, particle concentration and nanoparticle arrangement forming aggregates in the effective magnetic anisotropy of Mn-Zn ferrite-based nanoparticles. Electron magnetic resonance and coercivity temperature dependence analyses, were critically compared for the estimation of the anisotropy. We found that the temperature dependence of the anisotropy follows the Callen-Callen model, while the symmetry depends on the particle concentration. At low concentration one observes only an uniaxial term, while increasing a cubic contribution has to be added. The effective anisotropy was found to increase the higher the particle concentration on magnetic colloids, as long as the easy axis was at the same direction of the nanoparticle chain. Increasing even further the concentration up to a highly packed condition (powder sample) one observes a decrease of the anisotropy, that was attributed to the random anisotropy axes configuration.
Backgorund: Non-invasive magnetic imaging techniques are necessary to assist assist magnetic nano... more Backgorund: Non-invasive magnetic imaging techniques are necessary to assist assist magnetic nanoparticles biomedical applications, mainly detecting their distribution inside the body. In Alternating Current Biosusceptometry (ACB), the magnetic nanoparticles magnetization response under an oscillating magnetic eld, which is applied through an excitation coil, is detected with a balanced detection coil system. Results: We built a Multi-Channel ACB system (MC-ACB) containing nineteen pick-up coils and obtained 2D quantitative images of magnetic nanoparticles distributions by solving an inverse problem. We reconstructed the magnetic nanoparticles spatial distributions in a eld of view of 14×14 cm² with a spatial resolution of 2.0 cm and sensitivity in the milligram scale. A correlation coe cient between quantitative reconstructed and nominal magnetic nanoparticles distributions above 0.6 was found for all measurements. Conclusion: Besides other interesting features such as su cient large eld of view dimension for mice and rat studies, portability, and the ability to assess the quantitative magnetic nanoparticles distributions in real-time, the MC-ACB system is a promising tool for quantitative imaging of magnetic nanoparticles distributions in real-time, offering an affordable setup for easy access in clinical or laboratory environments.
Inducing immunogenic cell death (ICD) during cancer therapy is a major challenge that might signi... more Inducing immunogenic cell death (ICD) during cancer therapy is a major challenge that might significantly improve patient survival. The purpose of this study was to develop a theranostic nanocarrier, capable both of conveying a cytotoxic thermal dose when mediating photothermal therapy (PTT) after its intravenous delivery, and of consequently inducing ICD, improving survival. The nanocarrier consists of red blood cell membranes (RBCm) embedding the near-infrared dye IR-780 (IR) and camouflaging Mn-ferrite nanoparticles (RBCm-IR-Mn). The RBCm-IR-Mn nanocarriers were characterized by size, morphology, surface charge, magnetic, photophysical, and photothermal properties. Their photothermal conversion efficiency was found to be size- and concentration-dependent. Late apoptosis was observed as the cell death mechanism for PTT. Calreticulin and HMGB1 protein levels increased for in vitro PTT with temperature around 55 °C (ablative regime) but not for 44 °C (hyperthermia), suggesting ICD e...
Biomimetic nanoparticles hold great promise for photonic-mediated nanomedicine due to the associa... more Biomimetic nanoparticles hold great promise for photonic-mediated nanomedicine due to the association of the biological functionality of the membrane with the physical/chemical goals of organic/inorganic structures, but studies involving fluorescent biomimetic vesicles are still scarce. The purpose of this article is to determine how photothermal therapy (PTT) with theranostic IR-780-based nanoparticles depends on the dye content, cholesterol content, lipid bilayer phase and cell membrane type. The photophysical responses of synthetic liposomes, cell membrane vesicles and hybrid nanoparticles are compared. The samples were characterized by nanoparticle tracking analysis, photoluminescence, electron spin resonance, and photothermal- and heat-mediated drug release experiments, among other techniques. The photothermal conversion efficiency (PCE) was determined using Roper’s method. All samples excited at 804 nm showed three fluorescence bands, two of them independent of the IR-780 cont...
Since magnetic nanoparticles (MNPs) have been used as multifunctional probes to diagnose and trea... more Since magnetic nanoparticles (MNPs) have been used as multifunctional probes to diagnose and treat liver diseases in recent years, this study aimed to assess how the condition of cirrhosis-associated hepatocarcinogenesis alters the biodistribution of hepatic MNPs. Using a real-time image acquisition approach, the distribution profile of MNPs after intravenous administration was monitored using an AC biosusceptometry (ACB) assay. We assessed the biodistribution profile based on the ACB images obtained through selected regions of interest (ROIs) in the heart and liver position according to the anatomical references previously selected. The signals obtained allowed for the quantification of pharmacokinetic parameters, indicating that the uptake of hepatic MNPs is compromised during liver cirrhosis, since scar tissue reduces blood flow through the liver and slows its processing function. Since liver monocytes/macrophages remained constant during the cirrhotic stage, the increased intrah...
This study investigated the fabrication of spherical gold shelled maghemite nanoparticles for use... more 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 bes...
Doxorubicin (DOX) is a chemotherapeutic agent commonly used for the treatment of solid tumors. Ho... more 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 nanopa...
Once administered in an organism, the physiological parameters of magnetic nanoparticles (MNPs) m... more Once administered in an organism, the physiological parameters of magnetic nanoparticles (MNPs) must be addressed, as well as their possible interactions and retention and elimination profiles. Alternating current biosusceptometry (ACB) is a biomagnetic detection system used to detect and quantify MNPs. The aims of this study were to evaluate the biodistribution and clearance of MNPs profiles through long-time in vivo analysis and determine the elimination time carried out by the association between the ACB system and MnFe2O4 nanoparticles. The liver, lung, spleen, kidneys, and heart and a blood sample were collected for biodistribution analysis and, for elimination analysis, and over 60 days. During the period analyzed, the animal’s feces were also collectedd. It was possible to notice a higher uptake by the liver and the spleen due to their characteristics of retention and uptake. In 60 days, we observed an absence of MNPs in the spleen and a significant decay in the liver. We als...
The generation of topological magnetic vortex-domain structures in iron-oxide nanomaterials has p... more 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 Fe 3 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 Fe 3+ and 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.
The use of magnetic nanoparticles (MNPs) in biomedical applications requires the quantitative kno... more The use of magnetic nanoparticles (MNPs) in biomedical applications requires the quantitative knowledge of their quantitative distribution within the body. AC Biosusceptometry (ACB) is a biomagnetic technique recently employed to detect MNPs in vivo by measuring the MNPs response when exposed to an alternate magnetic field. The ACB technique presents some interesting characteristics: non-invasiveness, low operational cost, high portability, and no need for magnetic shielding. ACB conventional methods until now provided only qualitative information about the MNPs’ mapping in small animals. We present a theoretical model and experimentally demonstrate the feasibility of ACB reconstructing 2D quantitative images of MNPs’ distributions. We employed an ACB single-channel scanning approach, measuring at 361 sensor positions, to reconstruct MNPs’ spatial distributions. For this, we established a discrete forward problem and solved the ACB system’s inverse problem. Thus, we were able to det...
Purpose: Noninvasive thermometry during magnetic nanoparticle hyperthermia (MNH) remains a challe... more Purpose: Noninvasive thermometry during magnetic nanoparticle hyperthermia (MNH) remains a challenge. Our pilot study proposes a methodology to determine the noninvasive intratumoral thermal dose during MNH in the subcutaneous tumor model. Methods: Two groups of Ehrlich bearing-mice with solid and subcutaneous carcinoma, a control group (n ¼ 6), and a MNH treated group (n ¼ 4) were investigated. Histopathology was used to evaluate the percentage of non-viable lesions in the tumor. MNH was performed at 301 kHz and 17.5 kA.m À1 , using a multifunctional nanocarrier. Surface temperature measurements were obtained using an infrared camera, where an ROI with 750 pixels was used for comparison with computer simulations. Realistic simulations of the bioheat equation were obtained by combining histopathology intratumoral lesion information and surface temperature agreement of at least 50% of the pixel's temperature data calculated and measured at the surface. Results: One animal of the MNH group showed tumor recurrence, while two others showed complete tumor remission (monitored for 585 days). Sensitivity analysis of the simulation parameters indicated low tumor blood perfusion. Numerical simulations indicated, for the animals with complete remission, an irreversible tissue injury of 91 ± 5% and 100%, while the one with recurrence had a lower value, 56 ± 7%. The computer simulations also revealed the in vivo heat efficiency of the nanocarrier. Conclusion: A new methodology for determining noninvasively the three-dimensional intratumoral thermal dose during MNH was developed. The method demonstrates the potential for predicting the long-term preclinical outcome of animals treated with MNH.
Isometric and anisometric iron oxide magnetic nanoparticles, synthesized via an eco-friendly rout... more Isometric and anisometric iron oxide magnetic nanoparticles, synthesized via an eco-friendly route, present modulated heating efficiency for magnetic hyperthermia applications.
The study demonstrates the performance of heating efficiency in single‐phase and binary phase spi... more The study demonstrates the performance of heating efficiency in single‐phase and binary phase spinel ferrite nanosystems. Ferrimagnetic cobalt ferrite (CoFe2O4) (CFO) and superparamagnetic copper ferrite/copper oxide (CuFe2O4/CuO) (CuF) nanosystems of different particle sizes were synthesized through a microwave‐assisted coprecipitation method. The heating behavior was observed in range of both field amplitudes (8‐24 kA/m at 516 kHz) and frequencies (325‐973 kHz at 12 kA/m). The heating efficiency was analyzed and compared by means of particle size, magnetization, effective anisotropy constant, and Néel relaxation mechanism. Indeed, the heating rate was maximized in larger ferrite particles with low effective anisotropy constant. Moreover, though the magnetization and effective anisotropy constant of single‐phase CoFe2O4 nanoparticles were higher, the binary phase CuFe2O4/CuO nanosystems of similar crystallite size (28 nm) exhibited superior heating efficiency (4.21°C/s). For a fiel...
The magnetic response of nanostructures plays an important role on biomedical applications being ... more The magnetic response of nanostructures plays an important role on biomedical applications being strongly influenced by the magnetic anisotropy. In this work we investigate the role of temperature, particle concentration and nanoparticle arrangement forming aggregates in the effective magnetic anisotropy of Mn-Zn ferrite-based nanoparticles. Electron magnetic resonance and coercivity temperature dependence analyses, were critically compared for the estimation of the anisotropy. We found that the temperature dependence of the anisotropy follows the Callen-Callen model, while the symmetry depends on the particle concentration. At low concentration one observes only an uniaxial term, while increasing a cubic contribution has to be added. The effective anisotropy was found to increase the higher the particle concentration on magnetic colloids, as long as the easy axis was at the same direction of the nanoparticle chain. Increasing even further the concentration up to a highly packed condition (powder sample) one observes a decrease of the anisotropy, that was attributed to the random anisotropy axes configuration.
Understanding high-field amplitude electromagnetic heat loss phenomena is of great importance, in... more Understanding high-field amplitude electromagnetic heat loss phenomena is of great importance, in particular, in the biomedical field, because 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 the 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, which is often obtained experimentally using a phenomenological allometric function. Experimental hyperthermia data with distinct ferrite-based nanoparticles and third harmonic magnetizati...
The dipolar interaction is known to substantially affect the properties of magnetic nanoparticles... more 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 inside nanocarriers. 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 important 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 solution, 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 PLGA nanospheres. We also introduce a simple technique to access the importance of the dipolar interaction in a given sample, based on the height of the AC susceptibility peaks for different driving frequencies. Our results help illustrate the important effect that the dipolar interaction has in most nanoparticle samples.
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Papers by ANDRIS BAKUZIS