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

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Lettuce is a vegetable that contributes vitamins, minerals, fibre, phenolic compounds and antioxidants to the human diet. In the search for improving production conditions and crop health, the use of microorganisms with plant growth-promoting capabilities, such as soil yeasts (PGPY), in conjunction with nanotechnology could offer sustainable development of agroecosystems. This study evaluated the synthesis of health-promoting bioactive compounds in lettuce under the application of soil yeast and an iron nanoparticle (NP-Fe2O3) encapsulated in alginate beads. Two yeast strains, Candida guillermondii and Rhodotorula mucilaginosa, and a consortium of both yeasts were used in the presence and absence of Fe2O3-NPs. Phenolic compounds were identified and quantified via HPLC-ESI-Q-ToF and antioxidant activity. Ten phenolic compounds were identified, highlighting the chicoric acid isomer and two quercetin glycosides with high concentrations of up to 100 µg g-1 in treatments with C. guillermondii. Treatments with R. mucilaginosa and NPs-Fe2O3 presented an increase in antioxidant activity, mainly in TEAC, CUPRAC and DPPH activities in leaves, with significant differences between treatments. Therefore, the use of encapsulated soil yeasts is a viable alternative for application in vegetables to improve the biosynthesis and accumulation of phenolic compounds in lettuce and other crops.

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This study synthesizes magnetic iron oxide nanoparticles from agro-waste sweet pepper extract, exploring their potential as antioxidant additives and in food preservation. Iron (III) chloride hexahydrate is the precursor, with sweet pepper extract as both a reducing and capping agent at pH 7.5. Characterization techniques, including microscopy and spectroscopy, analyze the sweet pepper extract-magnetic iron oxide nanoparticles. Antioxidant capacities against 2,2-diphenyl-1-picrylhydrazyl are assessed, incorporating nanoparticles into banana-based bioplastic for grape preservation. Microscopy reveals cubic and quasi-spherical structures, and spectroscopy confirms functional groups, including Fe-O bonds. X-ray diffraction identifies cubic and monoclinic magnetite with a monoclinic hematite presence. Sweet pepper extract exhibits 100% inhibitory activity in 20 min, while sweet pepper extract-magnetic iron oxide nanoparticles show an IC50 of 128.1 µg/mL. Furthermore, these nanoparticles, stabilized with banana-based bioplastic, effectively preserve grapes, resulting in a 27.4% lower weight loss rate after 144 h compared to the control group (34.6%). This pioneering study encourages institutional research into the natural antioxidant properties of agro-waste sweet pepper combined with magnetic iron and other metal oxide nanoparticles, offering sustainable solutions for nanopackaging and food preservation. Current research focuses on refining experimental parameters and investigating diverse applications for sweet pepper extract-magnetic iron oxide nanoparticles in varied contexts.

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Graphene-based nanomaterials (GBNMs), specifically graphene oxide (GO) and reduced graphene oxide (rGO), have shown great potential in cancer therapy owing to their physicochemical properties. As GO and rGO strongly absorb light in the near-infrared (NIR) region, they are useful in photothermal therapy (PTT) for cancer treatment. However, despite the structural similarities of GO and rGO, they exhibit different influences on anticancer treatment due to their different photothermal capacities. In this review, various characterization techniques used to compare the structural features of GO and rGO are first outlined. Then, a comprehensive summary and discussion of the applicability of GBNMs in the context of PTT for diverse cancer types are presented. This discussion includes the integration of PTT with secondary therapeutic strategies, with a particular focus on the photothermal capacity achieved through near-infrared irradiation parameters and the modifications implemented. Furthermore, a dedicated section is devoted to studies on hybrid magnetic-GBNMs. Finally, the challenges and prospects associated with the utilization of GBNM in PTT, with a primary emphasis on the potential for clinical translation, are addressed.

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Contamination of water by toxic dyes is a serious environmental problem. Adsorbents prepared by an environmentally safe route have stood out for application in pollutant removal. Herein, iron oxide-based nanomaterial composed of Fe(III)-OOH and Fe(II/III) bound to proanthocyanidins, with particles in the order of 20 nm, was prepared by green synthesis assisted by extract of açaí (Euterpe oleracea Mart.) berry seeds from an agro-industrial residue. The nanomaterial was applied in the adsorption of cationic dyes. Screening tests were carried out for methylene blue (MB), resulting in an outstanding maximum adsorption capacity of 531.8 mg g-1 at 343 K, pH 10, 180 min. The kinetics followed a pseudo-second-order model and the isotherm of Fritz-Schülnder provided the best fit. Thermodynamic data show an endothermic process with entropy increase, typical of chemisorption. The proposed mechanism is based on the multilayer formation over a heterogeneous adsorbent surface, with chemical and electrostatic interactions of MB with the iron oxide nanoparticles and with the proanthocyanidins. The high adsorption efficiency was attributed to the network formed by the polymeric proanthocyanidins that entangled and protected the iron oxide nanoparticles, which allowed the reuse of the nanomaterial for seven cycles without loss of adsorption efficiency.

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OBJECTIVES: This study assembled and characterized a dual nanocarrier of chlorhexidine (CHX) and fluconazole (FLZ), and evaluated its antibiofilm and cytotoxic effects. METHODS: CHX and FLZ were added to iron oxide nanoparticles (IONPs) previously coated by chitosan (CS) and characterized by physical-chemical analyses. Biofilms from human saliva supplemented with Candida species were grown (72 h) on glass discs and treated (24 h) with IONPs-CS carrying CHX (at 39, 78, or 156 µg/mL) and FLZ (at 156, 312, or 624 µg/mL) in three growing associations. IONPs and CS alone, and 156 µg/mL CHX + 624 µg/mL FLZ (CHX156-FLZ624) were tested as controls. Next, microbiological analyses were performed. The viability of human oral keratinocytes (NOKsi lineage) was also determined (MTT reduction assay). Data were submitted to ANOVA or Kruskal-Wallis, followed by Fisher's LSD or Tukey's tests (α=0.05). RESULTS: Nanocarriers with spherical-like shape and diameter around 6 nm were assembled, without compromising the crystalline property and stability of IONPs. Nanocarrier at the highest concentrations was the most effective in reducing colony-forming units of Streptococcus mutans, Lactobacillus spp., Candida albicans, and Candida glabrata. The other carriers and CHX156-FLZ624 showed similar antibiofilm effects, and significantly reduced lactic acid production (p<0.001). Also, a dose-dependent cytotoxic effect against oral keratinocytes was observed for the dual nanocarrier. IONPs-CS-CHX-FLZ and CHX-FLZ significantly reduced keratinocyte viability at CHX and FLZ concentrations ≥7.8 and 31.25 µg/mL, respectively (p<0.05). CONCLUSION: The nanotherapy developed outperformed the effect of the combination CHX-FLZ on microcosm biofilms, without increasing the cytotoxic effect of the antimicrobials administered. CLINICAL SIGNIFICANCE: The dual nanocarrier is a promising topically-applied therapy for the management of oral candidiasis considering that its higher antibiofilm effects allow the use of lower concentrations of antimicrobials than those found in commercial products.

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Bone marrow transplantation is a treatment for a variety of hematological and non-hematological diseases. For the transplant success, it is mandatory to have a thriving engraftment of transplanted cells, which directly depends on their homing. The present study proposes an alternative method to evaluate the homing and engraftment of hematopoietic stem cells using bioluminescence imaging and inductively coupled plasma mass spectrometry (ICP-MS) associated with superparamagnetic iron oxide nanoparticles. We have identified an enriched population of hematopoietic stem cells in the bone marrow following the administration of Fluorouracil (5-FU). Lately, the cell labeling with nanoparticles displayed the greatest internalization status when treated with 30 µg Fe/mL. The quantification by ICP-MS evaluate the stem cells homing by identifying 3.95 ± 0.37 µg Fe/mL in the control and 6.61 ± 0.84 µg Fe/mL in the bone marrow of transplanted animals. In addition, 2.14 ± 0.66 mg Fe/g in the spleen of the control group and 2.17 ± 0.59 mg Fe/g in the spleen of the experimental group was also measured. Moreover, the bioluminescence imaging provided the follow up on the hematopoietic stem cells behavior by monitoring their distribution by the bioluminescence signal. Lastly, the blood count enabled the monitoring of animal hematopoietic reconstitution and ensured the transplantation effectiveness.

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Magnetic nanoparticles based on iron oxides (MNPs-Fe) have been proposed as photothermal agents (PTAs) within antibacterial photothermal therapy (PTT), aiming to counteract the vast health problem of multidrug-resistant bacterial infections. We present a quick and easy green synthesis (GS) to prepare MNPs-Fe harnessing waste. Orange peel extract (organic compounds) was used as a reducing, capping, and stabilizing agent in the GS, which employed microwave (MW) irradiation to reduce the synthesis time. The produced weight, physical-chemical features and magnetic features of the MNPs-Fe were studied. Moreover, their cytotoxicity was assessed in animal cell line ATCC RAW 264.7, as well as their antibacterial activity against Staphylococcus aureus and Escherichia coli. We found that the 50GS-MNPs-Fe sample (prepared by GS, with 50% v/v of NH4OH and 50% v/v of orange peel extract) had an excellent mass yield. Its particle size was ~50 nm with the presence of an organic coating (terpenes or aldehydes). We believe that this coating improved the cell viability in extended periods (8 days) of cell culture with concentrations lower than 250 µg·mL-1, with respect to the MNPs-Fe obtained by CO and single MW, but it did not influence the antibacterial effect. The bacteria inhibition was attributed to the plasmonic of 50GS-MNPs-Fe (photothermal effect) by irradiation with red light (630 nm, 65.5 mW·cm-2, 30 min). We highlight the superparamagnetism of the 50GS-MNPs-Fe over 60 K in a broader temperature range than the MNPs-Fe obtained by CO (160.09 K) and MW (211.1 K). Therefore, 50GS-MNPs-Fe could be excellent candidates as broad-spectrum PTAs in antibacterial PTT. Furthermore, they might be employed in magnetic hyperthermia, magnetic resonance imaging, oncological treatments, and so on.

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Breast cancer is the most commonly diagnosed type of cancer among the female population worldwide. It is a disease with a high incidence and geographic distribution that negatively impacts global public health and deleteriously affect the quality of life of cancer patients. Among the new approaches, cancer immunotherapy is the most promising trend in oncology by stimulating the host's own immune system to efficiently destroy cancer cells. Recent evidence has indicated that iron oxide nanoparticles can promote the reprograming of M2 into M1 macrophages with anti-tumor effects in the tumor microenvironment. Thus, the aim of the present work was to evaluate the ability of polyaniline-coated maghemite (Pani/γ-Fe2O3) nanoparticles to modulate human macrophages in 2D monolayers and 3D multicellular breast cancer models. It was observed that Pani/γ-Fe2O3 NPs re-educated IL-10-stimulated macrophages towards a pro-inflammatory profile, decreasing the proportion of CD163+ and increasing the CD86+ proportion in 2D models. NPs were successfully taken-up by macrophages presented in the 3D model and were also able to induce an increasing in their CD86+ proportion in triple MCTs model. Overall, our findings open new perspectives on the use of Pani/γ-Fe2O3 NPs as an immunomodulatory therapy for macrophage reprogramming towards an anti-tumor M1 phenotype, providing a new tool for breast cancer immunotherapies.

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A promise of cancer nanomedicine is the "targeted" delivery of therapeutic agents to tumors by the rational design of nanostructured materials. During the past several decades, a realization that in vitro and in vivo preclinical data are unreliable predictors of successful clinical translation has motivated a reexamination of this approach. Mathematical models of drug pharmacokinetics (PK) and biodistribution (BD) are essential tools for small-molecule drugs development. A key assumption underlying these models is that drug-target binding kinetics dominate blood clearance, hence recognition by host innate immune cells is not explicitly included. Nanoparticles circulating in the blood are conspicuous to phagocytes, and inevitable interactions typically trigger active biological responses to sequester and remove them from circulation. Our recent findings suggest that, instead of referring to nanoparticles as designed for active or passive "tumor targeting", we ought rather to refer to immune cells residing in the tumor microenvironment (TME) as active or passive actors in an essentially "cell-mediated tumor retention" process that competes with active removal by other phagocytes. Indeed, following intravenous injection, nanoparticles induce changes in the immune compartment of the TME because of nanoparticle uptake, irrespective of the nature of tumor targeting moieties. In this study, we propose a 6-compartment PK model as an initial mathematical framework for modeling this tumor-associated immune cell-mediated retention. Published in vivo PK and BD results obtained with bionized nanoferrite® (BNF®) nanoparticles were combined with results from in vitro internalization experiments with murine macrophages to guide simulations. As a preliminary approximation, we assumed that tumor-associated macrophages (TAMs) are solely responsible for active retention in the TME. We model the TAM approximation by relating in vitro macrophage uptake to an effective macrophage avidity term for the BNF® nanoparticles under consideration.

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