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1.
ACS Appl Mater Interfaces ; 16(12): 15457-15478, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38483821

RESUMO

The surface modification of magnetite nanoparticles (Fe3O4 NPs) is a promising approach to obtaining biocompatible and multifunctional nanoplatforms with numerous applications in biomedicine, for example, to fight cancer. However, little is known about the effects of Fe3O4 NP-associated reductive stress against cancer cells, especially against chemotherapy-induced drug-resistant senescent cancer cells. In the present study, Fe3O4 NPs in situ coated by dextran (Fe3O4@Dex) and glucosamine-based amorphous carbon coating (Fe3O4@aC) with potent reductive activity were characterized and tested against drug-induced senescent breast cancer cells (Hs 578T, BT-20, MDA-MB-468, and MDA-MB-175-VII cells). Fe3O4@aC caused a decrease in reactive oxygen species (ROS) production and an increase in the levels of antioxidant proteins FOXO3a, SOD1, and GPX4 that was accompanied by elevated levels of cell cycle inhibitors (p21, p27, and p57), proinflammatory (NFκB, IL-6, and IL-8) and autophagic (BECN1, LC3B) markers, nucleolar stress, and subsequent apoptotic cell death in etoposide-stimulated senescent breast cancer cells. Fe3O4@aC also promoted reductive stress-mediated cytotoxicity in nonsenescent breast cancer cells. We postulate that Fe3O4 NPs, in addition to their well-established hyperthermia and oxidative stress-mediated anticancer effects, can also be considered, if modified using amorphous carbon coating with reductive activity, as stimulators of reductive stress and cytotoxic effects in both senescent and nonsenescent breast cancer cells with different gene mutation statuses.


Assuntos
Antineoplásicos , Neoplasias da Mama , Hipertermia Induzida , Nanopartículas de Magnetita , Nanopartículas , Humanos , Feminino , Linhagem Celular Tumoral , Carbono/farmacologia , Neoplasias da Mama/tratamento farmacológico , Compostos Férricos/farmacologia , Antineoplásicos/farmacologia , Autofagia , Nanopartículas Magnéticas de Óxido de Ferro
2.
ACS Appl Mater Interfaces ; 16(9): 11251-11262, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38394459

RESUMO

Nanozyme has been proven to be an attractive and promising candidate to alleviate the current pressing medical problems. However, the unknown clinical safety and limited function beyond the catalysis of the most reported nanozymes cannot promise an ideal therapeutic outcome in further clinical application. Herein, we find that ferric maltol (FM), a clinically approved iron supplement synthesized through a facile scalable method, exhibits excellent peroxidase-like activity than natural horseradish peroxidase-like (HRP) and commonly reported Fe-based nanozymes, and also shows high antibacterial performance for methicillin-resistant Staphylococcus aureus (MRSA) elimination (100%) and wound disinfection. In addition, with added effects inherited from contained maltol, FM can accelerate skin barrier recovery. Therefore, the exploration of FM as a safe and desired nanozyme provides a timely alternative to current antibiotic therapy against drug-resistant bacteria.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Pironas , Desinfecção , Compostos Férricos/farmacologia , Peroxidase do Rábano Silvestre , Catálise , Antibacterianos/farmacologia , Peróxido de Hidrogênio , Peroxidase
3.
PLoS One ; 18(3): e0282443, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36893115

RESUMO

Saussurea costus is from medicinal plants and have therapeutic properties that were recorded in a variety of medical functions. The usage of biomaterials in the synthesis of nanoparticles is an essential strategy in green nanotechnology. Iron oxide nanoparticles (IONPs) were composed in the stage of (2:1, FeCl2: FeCl3) solution by using the aqueous extract of Saussurea costus peel in an eco-friendly method to evaluate their antimicrobial property. The properties of the obtained IONPs were evaluated using a scanning (SEM) and transmission (TEM) electron microscope. The mean size of IONPs discovered by Zetasizer varies between 100 and 300 nm, with a mean particle size of 295 nm. The morphology of IONPs (γ-Fe2O3) was determined to be nearly spherical and prismatic-curved. Moreover, the antimicrobial property of IONPs was assessed with nine pathogenic microbes, revealing that the nanoparticles have antimicrobial activities with Pseudomonas aeruginosa, Escherichia coli, Shigella sp., Staphylococcus sp. and Aspergillus niger, with possible applications in the therapeutic and biomedical fields.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Saussurea , Compostos Férricos/farmacologia , Extratos Vegetais/farmacologia , Anti-Infecciosos/farmacologia , Nanopartículas Magnéticas de Óxido de Ferro
4.
Anaesth Crit Care Pain Med ; 42(1): 101171, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36375780

RESUMO

BACKGROUND: Perioperative anemia is common in cardiac surgery. Few studies investigated the effect of postoperative intravenous (IV) iron supplementation and were mostly inconclusive. METHODS: Design: A randomized single-center, double-blind, placebo-controlled, parallel-group trial. PARTICIPANTS: 195 non-anemic patients were recruited from December 2018 to December 2020: 97 patients received 1 g of ferric carboxymaltose (FCM) and 98 patients received 100 mL of physiological serum on postoperative day 1. MEASUREMENTS: hemoglobin levels, reticulocyte count, serum iron, serum ferritin, and transferrin saturation were measured at induction of anesthesia, postoperative days 1, 5, and 30. Transfusion rate, duration of mechanical ventilation, critical care unit length of stay, and side effects associated with IV iron administration were measured. The primary outcome was hemoglobin level on day 30. Secondary outcomes included iron balance, transfused red cell packs, and critical care unit length of stay. RESULTS: At day 30, the hemoglobine level was higher in the FCM group than in the placebo group (mean 12.9 ± 1.2 vs. 12.1 ± 1.3 g/dL (95%CI 0.41-1.23, p-value <0.001)). Patients in the FCM group received fewer blood units (median 1[0-2] unit vs. 2 [0-3] units, p-value = 0.037) and had significant improvement in iron balance compared to the control group. No side effects associated with FCM administration were reported. CONCLUSION: In this randomized controlled trial, administration of FCM on postoperative day 1 in non-anemic patients undergoing cardiac surgery increased hemoglobin levels by 0.8 g/dL on postoperative day 30, leading to reduced transfusion rate, and improved iron levels on postoperative day 5 and 30. CLINICAL TRIAL REGISTRY NUMBER: NCT03759964.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Compostos Férricos , Humanos , Compostos Férricos/uso terapêutico , Compostos Férricos/farmacologia , Ferro , Hemoglobinas
5.
Sci Rep ; 12(1): 6695, 2022 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-35461329

RESUMO

In chronic kidney disease, ferric citrate has been shown to be an effective phosphate binder and source of enteral iron; however, the effects of ferric citrate on the kidney have been less well-studied. Here, in Col4α3 knockout mice-a murine model of progressive chronic kidney disease, we evaluated the effects of five weeks of 1% ferric citrate dietary supplementation. As expected, ferric citrate lowered serum phosphate concentrations and increased serum iron levels in the Col4α3 knockout mice. Consistent with decreased enteral phosphate absorption and possibly improved iron status, ferric citrate greatly reduced circulating fibroblast growth factor 23 levels. Interestingly, ferric citrate also lessened systemic inflammation, improved kidney function, reduced albuminuria, and decreased kidney inflammation and fibrosis, suggesting renoprotective effects of ferric citrate in the setting of chronic kidney disease. The factors mediating possible ferric citrate renoprotection, the mechanisms by which they may act, and whether ferric citrate affects chronic kidney disease progression in humans deserves further study.


Assuntos
Compostos Férricos , Insuficiência Renal Crônica , Animais , Modelos Animais de Doenças , Feminino , Compostos Férricos/farmacologia , Humanos , Inflamação , Ferro , Masculino , Camundongos , Camundongos Knockout , Fosfatos
6.
Sci Rep ; 12(1): 2792, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35181698

RESUMO

Food fortification with iron nanoparticles (NPs) could help prevent iron deficiency anemia, but the absorption pathway and biodistribution of iron-NPs and their bioavailability in humans is unclear. Dietary non-heme iron is physiologically absorbed via the divalent metal transporter-1 (DMT1) pathway. Using radio- iron isotope labelling in mice with a partial knockdown of intestine-specific DMT1, we assessed oral absorption and tissue biodistribution of nanostructured ferric phosphate (FePO4-NP; specific surface area [SSA] 98 m2g-1) compared to to ferrous sulfate (FeSO4), the reference compound. We show that absorption of iron from FePO4-NP appears to be largely DMT1 dependent and that its biodistribution after absorption is similar to that from FeSO4, without abnormal deposition of iron in the reticuloendothelial system. Furthermore, we demonstrate high bioavailability from iron NPs in iron deficient anemic women in a randomized, cross-over study using stable-isotope labelling: absorption and subsequent erythrocyte iron utilization from two 57Fe-labeled FePO4-NP with SSAs of 98 m2g-1 and 188 m2g-1 was 2.8-fold and 5.4-fold higher than from bulk FePO4 with an SSA of 25 m2g-1 (P < 0.001) when added to a rice and vegetable meal consumed by iron deficient anemic women. The FePO4-NP 188 m2g-1 achieved 72% relative bioavailability compared to FeSO4. These data suggest FePO4-NPs may be useful for nutritional applications.


Assuntos
Anemia Ferropriva/dietoterapia , Proteínas de Transporte de Cátions/genética , Compostos Férricos/farmacologia , Ferro/metabolismo , Adsorção/efeitos dos fármacos , Adulto , Anemia Ferropriva/genética , Anemia Ferropriva/metabolismo , Anemia Ferropriva/patologia , Animais , Disponibilidade Biológica , Suplementos Nutricionais/efeitos adversos , Feminino , Compostos Férricos/química , Compostos Ferrosos/farmacologia , Alimentos Fortificados/efeitos adversos , Humanos , Ferro/farmacologia , Radioisótopos de Ferro/farmacologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Nanoestruturas/uso terapêutico , Adulto Jovem
7.
Biochim Biophys Acta Mol Basis Dis ; 1868(1): 166287, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34626772

RESUMO

Oxidative stress and lipid peroxidation are major causes of skin injury induced by ultraviolet (UV) irradiation. Ferroptosis is a form of regulated necrosis driven by iron-dependent peroxidation of phospholipids and contributes to kinds of tissue injuries. However, it remains unclear whether the accumulation of lipid peroxides in UV irradiation-induced skin injury could lead to ferroptosis. We generated UV irradiation-induced skin injury mice model to examine the accumulation of the lipid peroxides and iron. Lipid peroxides 4-HNE, the oxidative enzyme COX2, the oxidative DNA damage biomarker 8-OHdG, and the iron level were increased in UV irradiation-induced skin. The accumulation of iron and lipid peroxidation was also observed in UVB-irradiated epidermal keratinocytes without actual ongoing ferroptotic cell death. Ferroptosis was triggered in UV-irradiated keratinocytes stimulated with ferric ammonium citrate (FAC) to mimic the iron overload. Although GPX4 protected UVB-injured keratinocytes against ferroptotic cell death resulted from dysregulation of iron metabolism and the subsequent increase of lipid ROS, keratinocytes enduring constant UVB treatment were markedly sensitized to ferroptosis. Nicotinamide mononucleotide (NMN) which is a direct and potent NAD+ precursor supplement, rescued the imbalanced NAD+/NADH ratio, recruited the production of GSH and promoted resistance to lipid peroxidation in a GPX4-dependent manner. Taken together, our data suggest that NMN recruits GSH to enhance GPX4-mediated ferroptosis defense in UV irradiation-induced skin injury and inhibits oxidative skin damage. NMN or ferroptosis inhibitor might become promising therapeutic approaches for treating oxidative stress-induced skin diseases or disorders.


Assuntos
Glutationa/genética , Ferro/metabolismo , Estresse Oxidativo/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Pele/metabolismo , 8-Hidroxi-2'-Desoxiguanosina/farmacologia , Aldeídos/farmacologia , Animais , Ciclo-Oxigenase 2/genética , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Compostos Férricos/farmacologia , Ferroptose/efeitos dos fármacos , Ferroptose/efeitos da radiação , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos da radiação , Peróxidos Lipídicos/farmacologia , Camundongos , Mononucleotídeo de Nicotinamida/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Compostos de Amônio Quaternário/farmacologia , Pele/efeitos dos fármacos , Pele/lesões , Pele/patologia , Raios Ultravioleta/efeitos adversos
8.
Kidney Int ; 101(4): 711-719, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34838540

RESUMO

Ferric citrate is approved as an iron replacement product in patients with non-dialysis chronic kidney disease and iron deficiency anemia. Ferric citrate-delivered iron is enterally absorbed, but the specific mechanisms involved have not been evaluated, including the possibilities of conventional, transcellular ferroportin-mediated absorption and/or citrate-mediated paracellular absorption. Here, we first demonstrate the efficacy of ferric citrate in high hepcidin models, including Tmprss6 knockout mice (characterized by iron-refractory iron deficiency anemia) with and without adenine diet-induced chronic kidney disease. Next, to assess whether or not enteral ferric citrate absorption is dependent on ferroportin, we evaluated the effects of ferric citrate in a tamoxifen-inducible, enterocyte-specific ferroportin knockout murine model (Villin-Cre-ERT2, Fpnflox/flox). In this model, ferroportin deletion was efficient, as tamoxifen injection induced a 4000-fold decrease in duodenum ferroportin mRNA expression, with undetectable ferroportin protein on Western blot of duodenal enterocytes, resulting in a severe iron deficiency anemia phenotype. In ferroportin-deficient mice, three weeks of 1% ferric citrate dietary supplementation, a dose that prevented iron deficiency in control mice, did not improve iron status or rescue the iron deficiency anemia phenotype. We repeated the conditional ferroportin knockout experiment in the setting of uremia, using an adenine nephropathy model, where three weeks of 1% ferric citrate dietary supplementation again failed to improve iron status or rescue the iron deficiency anemia phenotype. Thus, our data suggest that enteral ferric citrate absorption is dependent on conventional enterocyte iron transport by ferroportin and that, in these models, significant paracellular absorption does not occur.


Assuntos
Anemia Ferropriva , Proteínas de Transporte de Cátions , Anemia Ferropriva/tratamento farmacológico , Animais , Proteínas de Transporte de Cátions/genética , Compostos Férricos/farmacologia , Hepcidinas/metabolismo , Humanos , Ferro/metabolismo , Camundongos
9.
Food Funct ; 12(23): 11819-11828, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34787162

RESUMO

Obesity is associated with an increased risk of an iron deficiency; however, a synergistic relationship between iron and lipid homeostasis was also observed. The aim of this study was to investigate the effects of pharmacological doses of iron supplementation on omega 3 (n-3) and omega 6 (n-6) polyunsaturated fatty acids (PUFAs). Sprague-Dawley (SD) rats were fed a normal diet or a 50% high-fat diet (HFD) without or with pharmacological doses of ferric citrate (0.25, 1, or 2 g ferric iron per kg diet) for 12 weeks, and erythrocyte profiles of n-3 and n-6 PUFAs were quantitated. Ferric citrate supplementation showed dose-related effects on liver inflammation, liver iron accumulation, and increasing circulating levels of iron, erythrocyte degradation biomarkers LVV-hemorphin-7, malondialdehyde (MDA), and insulin. Obese rats supplemented with 2 g ferric iron per kg diet also had decreased levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and total n-3 PUFAs compared to rats fed a normal diet or HFD alone. A western blotting analysis revealed that iron-mediated downregulation of n-3 PUFA-converting enzymes (Δ5 and Δ6 desaturases) only occurred at high dosages (≥1 g ferric iron per kg diet). A Spearman correlation analysis showed that total liver iron and serum LVV-hemorphin-7 and MDA were negatively correlated with n-3 PUFAs and their converting enzymes (Δ5 and Δ6 desaturases) (all p < 0.05). In conclusion, obese rats that received high-dose ferric citrate supplementation (>1 g of ferric iron per kg diet) exhibited decreased n-3 PUFA levels via downregulation of expressions of Δ5 and Δ6 desaturase enzymes.


Assuntos
Dessaturase de Ácido Graxo Delta-5/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Compostos Férricos , Linoleoil-CoA Desaturase/metabolismo , Obesidade/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Regulação para Baixo/efeitos dos fármacos , Compostos Férricos/administração & dosagem , Compostos Férricos/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley
10.
Int J Mol Sci ; 22(18)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34576090

RESUMO

Iron deficiency is the most common mammalian nutritional disorder. However, among mammalian species iron deficiency anemia (IDA), occurs regularly only in pigs. To cure IDA, piglets are routinely injected with high amounts of iron dextran (FeDex), which can lead to perturbations in iron homeostasis. Here, we evaluate the therapeutic efficacy of non-invasive supplementation with Sucrosomial iron (SI), a highly bioavailable iron supplement preventing IDA in humans and mice and various iron oxide nanoparticles (IONPs). Analysis of red blood cell indices and plasma iron parameters shows that not all iron preparations used in the study efficiently counteracted IDA comparable to FeDex-based supplementation. We found no signs of iron toxicity of any tested iron compounds, as evaluated based on the measurement of several toxicological markers that could indicate the occurrence of oxidative stress or inflammation. Neither SI nor IONPs increased hepcidin expression with alterations in ferroportin (FPN) protein level. Finally, the analysis of the piglet gut microbiota indicates the individual pattern of bacterial diversity across taxonomic levels, independent of the type of supplementation. In light of our results, SI but not IONPs used in the experiment emerges as a promising nutritional iron supplement, with a high potential to correct IDA in piglets.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Suplementos Nutricionais , Compostos Férricos/administração & dosagem , Compostos Férricos/uso terapêutico , Nanopartículas Magnéticas de Óxido de Ferro/administração & dosagem , Nanopartículas Magnéticas de Óxido de Ferro/química , Administração Oral , Anemia Ferropriva/sangue , Animais , Animais Recém-Nascidos , Biomarcadores/metabolismo , Duodeno/metabolismo , Compostos Férricos/farmacologia , Compostos Ferrosos/uso terapêutico , Hepcidinas/sangue , Hepcidinas/genética , Masculino , Microbiota , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Suínos
11.
J Food Sci ; 86(9): 3839-3854, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34337745

RESUMO

The study aimed to evaluate the physicochemical and functional properties of liquid whole egg (LWE) with L-calcium lactate (L-Ca), zinc lactate (L-Zn), and sodium ferric EDTA (NaFeEDTA), and to compare with NaCl addition to determine the application potential of these mineral supplements. Results showed that salts addition significantly influenced the foaming, emulsifying, and gelling properties of LWE, which was possible through affecting the pH, particle size, surface hydrophobicity, apparent viscosity, and solubility. The addition of all the four salts reduced pH but increased the d4,3 diameter of LWE. Additionally, the addition of 200 mM L-Ca and 6 mM L-Zn significantly improved the emulsifying capacity by 41.73% and 13.6%, the foaming capacity by 26.57% and 10%, and the protein solubility by 13.89% and 12.70%, respectively. In the meantime, mineral supplements tend to produce lower hardness gel, especially with 25 mM L-Ca and 8 mM L-Zn, and the hardness was decreased from 2401.13 to 1138.29 and 1175.59 g, respectively. A relative decrease in hardness was desirable in gelled egg products. Moreover, the addition of NaCl and L-Ca showed a higher redness and yellowness, but the addition of NaFeEDTA showed an undesirable color in dark brown, which may be not accepted by the public. In summary, L-Ca and L-Zn had great potential for application in LWE, which was more appropriate than adding NaCl. This study provides a basis for improving the functional properties of LWE products in the future. PRACTICAL APPLICATION: The addition of L-Ca and L-Zn to liquid whole egg (LWE) could improve the foaming and emulsifying capacity of LWE as well as produce a lower hardness gel, which may be more conducive to the production of cake, custards, and meat products. Meantime, it is more in line with people's pursuit of a healthy diet.


Assuntos
Compostos de Cálcio , Ovos , Compostos Férricos , Lactatos , Compostos de Cálcio/farmacologia , Ácido Edético/farmacologia , Ovos/análise , Compostos Férricos/farmacologia , Alimentos Fortificados/normas , Humanos , Lactatos/farmacologia , Zinco/química
12.
Nutrients ; 13(7)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209042

RESUMO

BACKGROUND AND AIMS: Altering dietary ferrous sulphate (FS) consumption exacerbates a murine model of colitis and alters the intestinal microbiome. We investigated the impact of oral ferric maltol (FM) and FS on mice with dextran sodium sulphate (DSS) induced colitis, and the microbiome of patients with iron deficiency. METHODS: Mice had acute colitis induced, with 2% DSS for 5 days, followed by water. During this period, groups of mice were fed standard chow (200 ppm iron, SC, n = 8), or SC with 200ppm FS supplementation (n = 16, FSS), or SC with 200 ppm FM supplementation (n = 16, FMS). Clinical, pathological and microbiome assessments were compared at days 1 and 10. Fecal bacterial gDNA was extracted and the microbiome assessed by sequencing. Statistical inferences were made using MacQIIME. Principal Coordinates Analysis were used to visualize beta-diversity cluster analysis. Ten patients with IDA were treated with FS, and six with inactive inflammatory bowel disease received FM, supplements for four weeks: pre- and mid-treatment fecal samples were collected: the microbiome was assessed (see above). RESULTS: In mice, after DSS treatment, there was a decrease in many genera in the SC and FSS groups: Lactobacillales increased in mice that received FMS. In humans, FS treatment led to an increase in five genera, but FM was not associated with any measurable change. The severity of DSS-induced colitis was greater with FSS than FMS. CONCLUSIONS: This study demonstrates differential and unique influences of ferric maltol and ferrous sulphate supplements on intestinal microbiota. These differences might contribute to the different side effects associated with these preparations.


Assuntos
Compostos Férricos/administração & dosagem , Compostos Férricos/farmacologia , Compostos Ferrosos/farmacologia , Pironas/administração & dosagem , Pironas/farmacologia , Administração Oral , Animais , Biodiversidade , Peso Corporal/efeitos dos fármacos , Colite/induzido quimicamente , Colite/microbiologia , Colite/patologia , Colo/efeitos dos fármacos , Colo/microbiologia , Colo/patologia , Sulfato de Dextrana , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Ferro/metabolismo , Camundongos Endogâmicos C57BL , Filogenia
13.
J Mater Chem B ; 9(22): 4510-4522, 2021 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-34027529

RESUMO

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research. The present study aims to design a nanoplatform that offers the opportunity to enhance antitumor activity while minimizing side effects. Given the Au-mediated X-ray radiation enhancement and the ability of Fe-based nanomaterials to create reactive oxygen species (ROS) and DNA damage, we anticipated that bimetallic Fe3O4-Au heterodimer would bring strong radiosensitizing capacity. Fe3O4-Au heterodimer surface was covered with bovine serum albumin (BSA) to achieve good surface functionality, stability and prolonged blood circulation. Folic acid (FA) moieties were added to the nanoformulation to increase tumor-homing, specificity and uptake. Finally, curcumin (CUR) was incorporated into the nanoparticle to function as a natural anticancer agent. The integration of all these components has yielded a single nanoplatform, Fe3O4-Au-BSA-FA-CUR, capable of successfully fulfilling the mission of superadditive cancer therapy to avoid the risks of organ removal surgery. The efficacy of the proposed nanoplatform was investigated in vitro and in vivo. High radiosensitizing ability, X-ray-induced ROS generation and DNA damage, and good biocompatibility were demonstrated through in vitro experiments. Also, the administration of Fe3O4-Au-BSA-FA-CUR with X-ray irradiation completely eradicated the tumor without any mortality and toxicity in healthy tissues in vivo. Our results highlight the potential of CUR-loaded Fe3O4-Au-BSA-FA heteronanostructure to enable synergistic localized radiochemotherapy and open up a new door to attractive possibilities that warrant further exploration.


Assuntos
Neoplasias da Mama/terapia , Compostos Férricos/farmacologia , Ouro/farmacologia , Radiossensibilizantes/farmacologia , Animais , Linhagem Celular Tumoral , Quimiorradioterapia , Camundongos
14.
Int J Med Sci ; 18(8): 1899-1909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33746607

RESUMO

The morbidity and mortality rates associated with non-small-cell lung carcinoma (NSCLC) are increasing every year, placing new demands on existing therapies and drugs. Ammonium ferric citrate (AFC) is often used as a food additive for iron supplementation; however, to our knowledge, no studies have investigated whether AFC can induce ferroptosis in NSCLC. In this study, we demonstrated that specific concentrations of AFC effectively inhibit the proliferation and invasion of lung cancer cell lines in vitro using a cell proliferation inhibition test, a transwell assay, and flow cytometry analysis of cell cycle and apoptosis. In addition, AFC significantly induced oxidative stress injury in lung cancer cell lines. A quantitative polymerase chain reaction assay showed that AFC markedly reduced the expression levels of cell growth factors, negative regulators of ferroptosis, and autophagy regulators. Lastly, a protein-protein interaction analysis revealed that glutathione peroxidase 4 (GPX4) exerted its biological role through the regulation of the GSS/GSR complex and downstream GGT family proteins. When the expression of GPX4 changes, its biological activities, such as the glutathione metabolic process, cellular biosynthetic process, cellular response to chemical stimulus, and antioxidant activity, change accordingly, thereby affecting the survival quality and physiological and biochemical activities of cells. Overall, this study verifies that AFC has the biological activity of activating oxidative stress injury in NSCLC cell lines, leading to a decrease in their autophagy and inducing ferroptosis. We also confirmed that the GPX4-GSS/GSR-GGT axis is a crucial target of AFC-induced ferroptosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Compostos Férricos/farmacologia , Ferroptose/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Compostos de Amônio Quaternário/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Férricos/uso terapêutico , Glutationa Redutase/metabolismo , Glutationa Sintase/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Estresse Oxidativo/efeitos dos fármacos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Compostos de Amônio Quaternário/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , gama-Glutamiltransferase/metabolismo
15.
Sci Rep ; 11(1): 3286, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558583

RESUMO

Iron oxide particles (IOP) are commonly used for Cellular Magnetic Resonance Imaging (MRI) and in combination with several treatments, like Magnetic Fluid Hyperthermia (MFH), due to the rise in temperature they provoke under an Alternating Magnetic Field (AMF). Micrometric IOP have a high sensitivity of detection. Nevertheless, little is known about their internalization processes or their potential heat power. Two micrometric commercial IOP (from Bangs Laboratories and Chemicell) were characterized by Transmission Electron Microscopy (TEM) and their endocytic pathways into glioma cells were analyzed. Their Specific Absorption Rate (SAR) and cytotoxicity were evaluated using a commercial AMF inductor. T2-weighted imaging was used to monitor tumor growth in vivo after MFH treatment in mice. The two micron-sized IOP had similar structures and r2 relaxivities (100 mM-1 s-1) but involved different endocytic pathways. Only ScreenMAG particles generated a significant rise in temperature following AMF (SAR = 113 W g-1 Fe). After 1 h of AMF exposure, 60% of ScreenMAG-labeled cells died. Translated to a glioma model, 89% of mice responded to the treatment with smaller tumor volume 42 days post-implantation. Micrometric particles were investigated from their characterization to their intracellular internalization pathways and applied in one in vivo cancer treatment, i.e. MFH.


Assuntos
Rastreamento de Células , Compostos Férricos , Glioma , Hipertermia Induzida , Imageamento por Ressonância Magnética , Animais , Linhagem Celular Tumoral , Compostos Férricos/farmacocinética , Compostos Férricos/farmacologia , Glioma/diagnóstico por imagem , Glioma/terapia , Humanos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Am J Hematol ; 96(5): 606-616, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33471363

RESUMO

Phosphorus has an essential role in cellular and extracellular metabolism; maintenance of normal phosphorus homeostasis is critical. Phosphorus homeostasis can be affected by diet and certain medications; some intravenous iron formulations can induce renal phosphate excretion and hypophosphatemia, likely through increasing serum concentrations of intact fibroblast growth factor 23. Case studies provide insights into two types of hypophosphatemia: acute symptomatic and chronic hypophosphatemia, while considering the role of pre-existing conditions and comorbidities, medications, and intravenous iron. This review examines phosphorus homeostasis and hypophosphatemia, with emphasis on effects of iron deficiency and iron replacement using intravenous iron formulations.


Assuntos
Hipofosfatemia/etiologia , Ferro/efeitos adversos , Fósforo/metabolismo , Anemia Hipocrômica/tratamento farmacológico , Calcitriol/fisiologia , Compostos Férricos/administração & dosagem , Compostos Férricos/efeitos adversos , Compostos Férricos/farmacologia , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/biossíntese , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/fisiologia , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Humanos , Hipofosfatemia/induzido quimicamente , Hipofosfatemia/diagnóstico , Hipofosfatemia/terapia , Infusões Parenterais , Ferro/administração & dosagem , Deficiências de Ferro , Rim/metabolismo , Síndromes de Malabsorção/complicações , Maltose/administração & dosagem , Maltose/efeitos adversos , Maltose/análogos & derivados , Maltose/farmacologia , Osteomalacia/etiologia , Hormônio Paratireóideo/fisiologia , Fósforo na Dieta/farmacocinética
17.
ACS Appl Bio Mater ; 4(5): 4280-4291, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35006840

RESUMO

The integration of multiple therapeutic and diagnostic functions into a single nanoplatform for image-guided cancer therapy has been an emerging trend in nanomedicine. We show here that multifunctional theranostic nanostructures consisting of superparamagnetic iron oxide (SPIO) and gold nanoparticles (AuNPs) scaffolded within graphene oxide nanoflakes (GO-SPIO-Au NFs) can be used for dual photo/radiotherapy by virtue of the near-infrared (NIR) absorbance of GO for photothermal therapy (PTT) and the Z element radiosensitization of AuNPs for enhanced radiation therapy (RT). At the same time, this nanoplatform can also be detected by magnetic resonance (MR) imaging because of the presence of SPIO NPs. Using a mouse carcinoma model, GO-SPIO-Au NF-mediated combined PTT/RT exhibited a 1.85-fold and 1.44-fold higher therapeutic efficacy compared to either NF-mediated PTT or RT alone, respectively, resulting in a complete eradication of tumors. As a sensitive multifunctional theranostic platform, GO-SPIO-Au NFs appear to be a promising nanomaterial for enhanced cancer imaging and therapy.


Assuntos
Antineoplásicos/farmacologia , Materiais Biocompatíveis/farmacologia , Carcinoma/tratamento farmacológico , Imageamento por Ressonância Magnética , Fototerapia , Radiossensibilizantes/farmacologia , Nanomedicina Teranóstica , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Carcinoma/metabolismo , Carcinoma/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Férricos/química , Compostos Férricos/farmacologia , Ouro/química , Ouro/farmacologia , Grafite/química , Grafite/farmacologia , Masculino , Teste de Materiais , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Tamanho da Partícula , Radiossensibilizantes/síntese química , Radiossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo
18.
Anticancer Agents Med Chem ; 21(13): 1767-1772, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33342418

RESUMO

BACKGROUND: The growing dissatisfaction with the available traditional chemotherapeutic agents has enhanced the need to develop new methods for obtaining materials with more effective and safe anti-cancer properties. Over the past few years, the usage of metallic nanoparticles has been a target for researchers of different scientific and commercial fields due to their tiny sizes, environment-friendly properties, and a wide range of applications. To overcome the obstacles of traditional physical and chemical methods for the synthesis of such nanoparticles, a new, less expensive, and eco-friendly method has been adopted using natural existing organisms as a reducing agent to mediate the synthesis of the desired metallic nanoparticles from their precursors, a process called green biosynthesis of nanoparticles. OBJECTIVE: In the present study, zinc-iron bimetallic nanoparticles (ZnFe2O4) were synthesized via an aqueous extract of Boswellia carteri resin mixed with zinc acetate and iron chloride precursors, and they were tested for their anticancer activity. METHODS: Various analytic methods were applied for the characterization of the phyto synthesized ZnFe2O4, and they were tested for their anticancer activity against MDA-MB-231, K562, MCF-7 cancer cell lines, and normal fibroblasts. RESULTS: Our results demonstrate the synthesis of cubic structured bimetallic nanoparticles ZnFe2O4 with an average diameter of 10.54 nm. MTT cytotoxicity assay demonstrates that our phyto-synthesized ZnFe2O4 nanoparticles exhibited a selective and potent anticancer activity against K562 and MDA-MB-231 cell lines with IC50 values 4.53 µM and 4.19 µM, respectively. CONCLUSION: In conclusion, our biosynthesized ZnFe2O4 nanoparticles show a promising, environmentally friendly, and low coast chemotherapeutic approach against selective cancers with a predicted low adverse side effect toward normal cells. Further, in vivo, advanced animal research should be done to execute their applicability in living organisms.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Boswellia/química , Compostos Férricos/farmacologia , Nanopartículas/química , Extratos Vegetais/farmacologia , Zinco/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Compostos Férricos/química , Compostos Férricos/isolamento & purificação , Humanos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade , Zinco/química , Zinco/isolamento & purificação
19.
Expert Rev Hematol ; 14(1): 7-29, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33317356

RESUMO

Introduction: Originally approved in Europe in 2009, ferric derisomaltose is the most recently authorized intravenous iron compound in the United States of America (2020). Ferric derisomaltose given as a rapid high-dose infusion can allow complete iron repletion in a single dose and it is now widely used in the treatment of iron deficiency. Areas covered: The chemistry, pharmacodynamics and pharmacokinetics of ferric derisomaltose are reviewed. Results from phase II, III and IV trials regarding efficacy and safety are presented. Mechanisms behind minor infusion reactions, hypersensitivity and hypophosphatemia are discussed. The economic impact of ferric derisomaltose use is presented. Data pertaining to the use of ferric derisomaltose in iron deficiency anemia, chronic kidney disease, inflammatory bowel disease, chronic heart failure, perioperative care and other patient groups are comprehensively covered. Expert opinion: Ferric derisomaltose is an effective intravenous iron formulation with a good safety profile, providing rapid, cost-effective iron repletion. Ferric derisomaltose releases low quantities of labile iron relative to older compounds. Anaphylaxis is extremely rare, and 'Fishbane' reactions are uncommon. Hypophosphatemia following ferric derisomaltose administration is infrequent in comparison to other intravenous irons such as ferric carboxymaltose. The scope of ferric derisomaltose use is growing with increasing research in these areas.


Assuntos
Anemia/tratamento farmacológico , Dissacarídeos/uso terapêutico , Animais , Ensaios Clínicos como Assunto , Dissacarídeos/efeitos adversos , Dissacarídeos/farmacocinética , Dissacarídeos/farmacologia , Controle de Medicamentos e Entorpecentes , Compostos Férricos/efeitos adversos , Compostos Férricos/farmacocinética , Compostos Férricos/farmacologia , Compostos Férricos/uso terapêutico , Humanos , Resultado do Tratamento
20.
Molecules ; 25(19)2020 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-32992439

RESUMO

Magnetic nanoparticles such as cobalt ferrite are investigated under clinical hyperthermia conditions for the treatment of cancer. Cobalt ferrite nanoparticles (CFNPs) synthesized by the thermal decomposition method, using nonionic surfactant Triton-X100, possess hydrophilic polyethylene oxide chains acting as reducing agents for the cobalt and iron precursors. The monodispersed nanoparticles were of 10 nm size, as confirmed by high-resolution transmission electron microscopy (HR-TEM). The X-ray diffraction patterns of CFNPs prove the existence of cubic spinel cobalt ferrites. Cs-corrected scanning transmission electron microscopy-high-angle annular dark-field imaging (STEM-HAADF) of CFNPs confirmed their multi-twinned crystallinity due to the presence of atomic columns and defects in the nanostructure. Magnetic measurements proved that the CFNPs possess reduced remnant magnetization (MR/MS) (0.86), which justifies cubic anisotropy in the system. Microwave-based hyperthermia studies performed at 2.45 GHz under clinical conditions in physiological saline increased the temperature of the CFNP samples due to the transformation of radiation energy to heat. The specific absorption rate of CFNPs in physiological saline was 68.28 W/g. Furthermore, when triple-negative breast cancer cells (TNBC) in the presence of increasing CFNP concentration (5 mg/mL to 40 mg/mL) were exposed to microwaves, the cell cytotoxicity was enhanced compared to CFNPs alone.


Assuntos
Antineoplásicos , Cobalto , Compostos Férricos , Hipertermia Induzida , Campos Magnéticos , Nanopartículas , Neoplasias de Mama Triplo Negativas/terapia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cobalto/química , Cobalto/farmacologia , Feminino , Compostos Férricos/síntese química , Compostos Férricos/química , Compostos Férricos/farmacologia , Humanos , Nanopartículas/química , Nanopartículas/uso terapêutico
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