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Made available in DSpace on 2022-04-29T08:35:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-10-01 Background: We evaluated the impacts of corona protein (CP) formation on the alternating current biosusceptometry (ACB) signal intensity and in vivo circulation times of three differently coated magnetic nanoparticles (MNP): bare, citrate-coated and bovine serum albumin-coated MNPs. Methods: We employed the ACB system, gel electrophoresis and mass spectrometry analysis. Results: Higher CP formation led to a greater reduction in the in vitro ACB signal intensity and circulation time. We found fewer proteins forming the CP for the bovine serum albumin-coated MNPs, which presented the highest circulation time in vivo among the MNPs studied. Conclusion: These data showed better biocompatibility, stability and magnetic signal uniformity in biological media for bovine serum albumin-coated MNPs than for citrate-coated MNPs and bare MNPs. Department of Biophysics and Pharmacology São Paulo State University, São Paulo Museum National d'Histoire Naturelle Institut de Minéralogie Physique des Matériaux et Cosmochimie IMPMC Sorbonne Université UMR 7590 CNRS Graduate Program in Tropical Diseases Botucatu Medical School (FMB) São Paulo State University (UNESP), São Paulo Biotechnology Institute São Paulo State University, São Paulo Institute of Physics and CNanoMed Federal University of Goiás Department of Biophysics and Pharmacology São Paulo State University, São Paulo Graduate Program in Tropical Diseases Botucatu Medical School (FMB) São Paulo State University (UNESP), São Paulo Biotechnology Institute São Paulo State University, São Paulo

The use of microwave-assisted synthesis (in water) of α-Fe2O3 nanomaterials followed by their transformation onto iron oxide Fe3O4-γ-Fe2O3 hollow nanoparticles encoding well-defined sizes and shapes [nanorings (NRs) and nanotubes (NTs)] is henceforth described. The impact of experimental variables such as concentration of reactants, volume of solvent employed, and reaction times/temperatures during the shape-controlled synthesis revealed that the key factor that gated generation of morphologically diverse nanoparticles was associated to the initial concentration of phosphate anions employed in the reactant mixture. All the nanomaterials presented were fully characterized by powder X-ray diffraction, field emission scanning electron microscopy, Fourier transform infrared, Mössbauer spectroscopy, and superconducting quantum interference device (SQUID). The hollow nanoparticles that expressed the most promising magnetic responses, NTs and NRs, were further tested in terms of efficiencies in controlling the magnetic hyperthermia, in view of their possible use for biomedical applications, supported by their excellent viability as screened by in vitro cytotoxicity tests. These systems NTs and NRs expressed very good magneto-hyperthermia properties, results that were further validated by micromagnetic simulations. The observed specific absorption rate (SAR) and intrinsic loss power of the NRs and NTs peaked the values of 340 W/g and 2.45 nH m2 kg–1 (NRs) and 465 W/g and 3.3 nH m2 kg–1 (NTs), respectively, at the maximum clinical field 450 Oe and under a frequency of 107 kHz and are the highest values among those reported so far in the hollow iron-oxide family. The higher SAR in NTs accounts the importance of magnetic shape anisotropy, which is well-predicted by the modified dynamic hysteresis (β-MDH) theoretical model., G.N. is thankful to Brazilian funding agency CAPES and PPGF-UFMA for providing doctorate fellowship and other financial support to visit UnB, Brasilia, UFG, Goiania, and CBPF, Rio de Janerio to perform the experiment, respectively. S.K.S. is very thankful to FAPEMA for the financial support. J.A.H.C. thanks to CNPq and FAPDF for the financial support. G.Z. thanks the support of the project “Development of preapplied research in nanotechnology and biotechnology” (no. CZ.02.1.01/0.0/0.0/17_048/0007323).

Multifunctional magnetic nanoparticles (NPs) that can generate and monitor heat (in real-time) during thermal therapy are a major challenge in nanomedicine. Here, we report a trimodal system combin...

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 = 6), and a MNH treated group (n = 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−1, 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.

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

Magnetic nanomaterials that respond to clinical magnetic devices have significant potential as cancer nanotheranostics. The complexities of their physics, however, introduce challenges for these applications. Hyperthermia is a heat-based cancer therapy that improves treatment outcomes and patient survival when controlled energy delivery is combined with accurate thermometry. To date, few technologies have achieved the needed evolution for the demands of the clinic. Magnetic fluid hyperthermia (MFH) offers this potential, but to be successful it requires particle-imaging technology that provides real-time thermometry. Presently, the only technology having the potential to meet these requirements is magnetic particle imaging (MPI), for which a proof-of-principle demonstration with MFH has been achieved. Successful clinical translation and adoption of integrated MPI/MFH technology will depend on successful resolution of the technological challenges discussed. This article is categorized under: Therapeutic Approaches and Drug DiscoveryNanomedicine for Oncologic Disease Diagnostic ToolsIn Vivo Nanodiagnostics and Imaging.

Made available in DSpace on 2022-04-28T19:52:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-03-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) 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 also determined the MNPs’ half-life through the liver and the spleen elimination. The data indicated a concentration decay profile over the 60 days, which suggests that, in addition to elimination via feces, there is an endogenous mechanism of metabolization or possible agglomeration of MNPs, resulting in loss of ACB signal intensity. Department of Biophysics and Pharmacology Institute of Biosciences São Paulo State University—UNESP, SP Institute of Physics Federal University of Goiás, GO Faculty of Philosophy Sciences and Letters at Ribeirão Preto University of São Paulo, SP Department of Biophysics and Pharmacology Institute of Biosciences São Paulo State University—UNESP, SP FAPESP: 2013/03258-9 FAPESP: 2015/1492.3-9 CNPq: 304107/2019-0 CNPq: 312074/2018-9 CAPES: 88882.432964/2019-01

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 determine the positions and quantities of MNPs in a field of view of 5×5×1&nbsp, cm3 with good precision and accuracy. The results show the ACB system’s capabilities to reconstruct the quantitative spatial distribution of MNPs with a spatial resolution better than 1&nbsp, cm, and a sensitivity of 1.17&nbsp, mg of MNPs fixed in gypsum. These results show the system’s potential for biomedical application of MNPs in several studies, for example, electrochemical-functionalized MNPs for cancer cell targeting, quantitative sensing, and possibly in vivo imaging.

Controlling populations of free-roaming dogs and cats poses a huge challenge worldwide. Non-surgical neutering strategies for male animals have been long pursued, but the implementation of the procedures developed has remained limited to date. As submitting the testes to high temperatures impairs spermatogenesis, the present study investigated localized application of magnetic nanoparticle hyperthermia (MNH) to the testicles as a potential non-surgical sterilization method for animals. An intratesticular injection of a magnetic fluid composed of manganese-ferrite nanoparticles functionalized with citrate was administered followed by testicle exposure to an alternate magnetic field to generate localized heat. Testicular MNH was highly effective, causing progressive seminiferous tubule degeneration followed by substitution of the parenchyma with stromal tissue and gonadal atrophy, suggesting an irreversible process with few side effects to general animal health.

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...

Recently, the development of an alternative magnetic refrigerant for the conventional fossil fuels attracts the researchers. We discussed the structural defect-induced magnetocaloric effect (MCE) i...

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.

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.Two groups of Ehrlich bearing-mice with solid and subcutaneous carcinoma, a control group (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 theA 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.

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 study demonstrates the performance of heating efficiency in single-phase and binary phase spinel ferrite nanosystems. Ferrimagnetic cobalt ferrite (CoFeO) (CFO) and superparamagnetic copper ferrite/copper oxide (CuFeO/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 CoFeO nanoparticles were higher, the binary phase CuFeO/CuO nanosystems of similar crystallite size (28 nm) exhibited superior heating efficiency (4.21°C/s). For a field amplitude and frequency of 24 kA/m and 516 kHz, the heating rate of CuF and CFO ferrites with different crystallite sizes decreased in the order of 4.21 > 2.14 > 0.58 > 0.52°C/s for 29 nm > 25 nm > 12 nm > 15 nm, respectively. The results emphasize that binary phase ferrite nanoparticles are better thermoseeds than the single-phase ferrites for the magnetic hyperthermia application., The authors greatly acknowledge FONDECYT Postdoctoral Research Project No.: 3160170, CONICYT PIA/APOYO CCTE AFB170007 and CONICYT BASAL CEDENNA FB0807, Government of Chile and FAPESP Postdoctoral Fellowship Process Number (2018) 19096-1, FAPESP thematic project number: 2017/10581-1, CNPq Grant number: 310230/2017-9, and FAPEG Grant number: 201710267000511, Government of Brazil for financial assistance

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.

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 Fe

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.

Bacteria resistant against various antimicrobial compounds have emerged in many countries, and the age of resistance has just started. Among the more promising novel antimicrobial compounds on which current research is focusing are the antimicrobial peptides (AMPs). These are often less susceptible to bacterial resistance since multiple modifications in the cellular membranes, cell wall and metabolism are required to reduce their effectiveness. Most likely, the use of pure AMPs will be insufficient for controlling pathogenic bacteria, and innovative approaches are required to employ AMPs in new antibiotic treatments. Therefore, here we review novel bionanotechnological approaches, including nanofibers, nanoparticles and magnetic particles for effectively using AMPs in fighting infectious diseases.

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 nanoparticle hyperthermia consists of an increase of the temperature of magnetic nanoparticles (heat centres) due to the interaction of their magnetic moments with an alternating magnetic field. In vivo experiments using this method usually use a few fibre-optic thermometers inserted in the animal body to monitor the heat deposition. As a consequence, only a few points of the 3D temperature distribution can be monitored by this invasive procedure. It is the purpose of this work to show that non-invasive infrared thermography is able to detect, in real time, magnetic nanoparticle hyperthermia as well as monitor the harmful field-induced eddy currents in a murine model with a subcutaneous tumour. This surface temperature measurement method has the potential to give information about the intratumoral temperature.The non-invasive magnetic hyperthermia experiments were performed at 300 kHz in non-uniform field configuration conditions in healthy mice and murine tumour induced by sarcoma S180. A soft ferrite-based biocompatible magnetic colloid consisting of manganese-ferrite nanoparticles surface-coated with citric acid were used in the experiments, which were extensively characterised by several techniques (transmission electron microscopy (TEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM)). The amplitude of the alternating magnetic fields was obtained from measurements using an AC field probe at similar experimental conditions. The temperature measurements were obtained from an infrared thermal camera and a fibre-optic thermometer.Three-minute magnetic hyperthermia experiments revealed surface temperature increase as high as 11 °K in healthy and (5 °K in S180 tumour) animals when injecting subcutaneously 2 mg of magnetic nanoparticles (86 μL of magnetic fluid), in contrast to around 1.5 °K (for healthy) and 2.5 °K (for cancerous) animals in experiments without the colloid due to field-induced eddy currents at the animal surface. The thermographic temperature measurements were found to agree with the fibre-optic measurements within a 5% error, and were associated with the skin emissivity angle of dependence in the experimental set-up. On the other hand, a 30-min magnetic nanoparticle hyperthermia revealed surface temperature increases as high as 12 °K close to the injection site, while above 2-3 cm no significant temperature increase was observed. Curiously, the intratumoral temperature, monitored by a fibre-optic sensor, was found to be almost the same as the thermal camera surface temperature after achieving an equilibrium temperature regime. From the observed isotherms at the animal surface, using an analytical heat conduction model, taking into account surface conductance, we estimate a magnetic heating power of 0.45 W/cm(3) and a specific loss power (SLP) of 85 W/g for a field of the order of only 10 kA/m at the injection site region.The results indicate that infrared thermography may be a promising tool for both early cancer detection and for hyperthermia treatment (at least for subcutaneous tumours), since the method permits access to information about the intratumoral temperature during a real-time magnetic hyperthermia as well as to estimate the in vivo nanoparticles SLP.

We review the use of Monte Carlo simulations in the description of magnetic nanoparticles dispersed in a liquid carrier. Our main focus is the use of theory and simulation as tools for the description of the properties of ferrofluids. In particular, we report on the influence of polydispersity and short-range interaction on the self-organization of nanoparticles. Such contributions are shown to be extremely important for systems characterized by particles with diameters smaller than 10 nm. A new 3D polydisperse Monte Carlo implementation for biocompatible magnetic colloids is proposed. As an example, theoretical and simulation results for an ionic-surfacted ferrofluid dispersed in a NaCl solution are directly compared to experimental data (transmission electron microscopy — TEM, magneto-transmissivity, and electron magnetic resonance — EMR). Our combined theoretical and experimental results suggest that during the aging process two possible mechanisms are likely to be observed: the nanoparticle's grafting decreases due to aggregate formation and the Hamaker constant increases due to oxidation. In addition, we also briefly discuss theoretical agglomerate formation models and compare them to experimental data.

Streptococcus mutans is the microorganism mostly responsible for initiation of tooth decay and also for the progression of an established lesion. Silver has been used for its antibacterial properties for many years, in different forms: ionised and elementary forms, as silver zeolites or as nanoparticles. The purpose of this study was to evaluate the antibacterial activity of three dental cements modified by nanosilver. Three cements were used: Sealapex, RelyX ARC, and Vitrebond. The cements were incorporated with 0.05 mL of silver nanoparticles solution. Control groups were prepared without silver. Six Petri plates with BHI were inoculated with S. mutans using sterile swabs. Three cavities were made in each agar plate (total = 18) and filled with the manipulated cements. They were incubated at 37°C for 48 h, and the inhibition halos were measured. The paired t-Test was used for statistical analysis (P<0.05). No inhibition halos were obtained for Sealapex and Rely X, but Vitrebond showed bactericidal activity without silver and enhanced effect with silver incorporation.