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1.
Luminescence ; 39(6): e4799, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38858760

ABSTRACT

In this study, tellurium-doped and undoped metal oxide nanoparticles (NPs) (ZnO, Mn3O4, SnO2) are compared, and a practical method for their synthesis is presented. Nanocomposites were created using the coprecipitation process, and comparisons between the three material categories under study were made using a range of characterization methods. The produced materials were subjected to structural, morphological, elemental composition, and functional group analyses using XRD, FESEM in combination with EDS, and FTIR. The optical characteristics in terms of cutoff wavelength were evaluated using UV-visible spectroscopy. Catalyzing the breakdown of methylene blue (MB) dye, the isolated nanocomposites demonstrated very consistent behavior when utilized as catalysts. Regarding both doped and undoped ZnO NPs, the maximum percentage of degradation was found to be 98% when exposed to solar Escherichia coli and Staphylococcus aureus, which stand for gram-positive and gram-negative bacteria, respectively, and were chosen as model strains for both groups using the disk diffusion technique in the context of in vitro antibacterial testing. Doped and undoped ZnO NPs exhibited greater antibacterial efficacy, with significant inhibition zones measuring 31.5 and 37.8 mm, compared with other metal oxide NPs.


Subject(s)
Anti-Bacterial Agents , Escherichia coli , Metal Nanoparticles , Microbial Sensitivity Tests , Staphylococcus aureus , Tellurium , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Tellurium/chemistry , Tellurium/pharmacology , Staphylococcus aureus/drug effects , Catalysis , Metal Nanoparticles/chemistry , Escherichia coli/drug effects , Photochemical Processes , Methylene Blue/chemistry , Methylene Blue/pharmacology , Zinc Oxide/chemistry , Zinc Oxide/pharmacology , Manganese/chemistry , Manganese/pharmacology , Tin/chemistry , Tin/pharmacology , Particle Size , Oxides/chemistry , Oxides/pharmacology
2.
Int J Nanomedicine ; 19: 5045-5056, 2024.
Article in English | MEDLINE | ID: mdl-38832334

ABSTRACT

Background: Chemodynamic therapy (CDT) is a new treatment approach that is triggered by endogenous stimuli in specific intracellular conditions for generating hydroxyl radicals. However, the efficiency of CDT is severely limited by Fenton reaction agents and harsh reaction conditions. Methods: Bimetallic PtMn nanocubes were rationally designed and simply synthesized through a one-step high-temperature pyrolysis process by controlling both the nucleation process and the subsequent crystal growth stage. The polyethylene glycol was modified to enhance biocompatibility. Results: Benefiting from the alloying of Pt nanocubes with Mn doping, the structure of the electron cloud has changed, resulting in different degrees of the shift in electron binding energy, resulting in the increasing of Fenton reaction activity. The PtMn nanocubes could catalyze endogenous hydrogen peroxide to toxic hydroxyl radicals in mild acid. Meanwhile, the intrinsic glutathione (GSH) depletion activity of PtMn nanocubes consumed GSH with the assistance of Mn3+/Mn2+. Upon 808 nm laser irradiation, mild temperature due to the surface plasmon resonance effect of Pt metal can also enhance the Fenton reaction. Conclusion: PtMn nanocubes can not only destroy the antioxidant system via efficient reactive oxygen species generation and continuous GSH consumption but also propose the photothermal effect of noble metal for enhanced Fenton reaction activity.


Subject(s)
Glutathione , Manganese , Platinum , Reactive Oxygen Species , Animals , Platinum/chemistry , Platinum/pharmacology , Reactive Oxygen Species/metabolism , Glutathione/chemistry , Humans , Manganese/chemistry , Manganese/pharmacology , Photothermal Therapy/methods , Mice , Metal Nanoparticles/chemistry , Hydrogen Peroxide/chemistry , Cell Line, Tumor , Hydroxyl Radical/chemistry , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Iron/chemistry
3.
Acta Biomater ; 181: 402-414, 2024 06.
Article in English | MEDLINE | ID: mdl-38734282

ABSTRACT

Tumor hypoxia, high oxidative stress, and low immunogenic create a deep-rooted immunosuppressive microenvironment, posing a major challenge to the therapeutic efficiency of cancer immunotherapy for solid tumor. Herein, an intelligent nanoplatform responsive to the tumor microenvironment (TME) capable of hypoxia relief and immune stimulation has been engineered for efficient solid tumor immunotherapy. The MnO2@OxA@OMV nanoreactor, enclosing bacterial-derived outer membrane vesicles (OMVs)-wrapped MnO2 nanoenzyme and the immunogenic cell death inducer oxaliplatin (OxA), demonstrated intrinsic catalase-like activity within the TME, which effectively catalyzed the endogenous H2O2 into O2 to enable a prolonged oxygen supply, thereby alleviating the tumor's oxidative stress and hypoxic TME, and expediting OxA release. The combinational action of OxA-caused ICD effect and Mn2+ from nanoreactor enabled the motivation of the cGAS-STING pathway to significantly improve the activation of STING and dendritic cells (DCs) maturation, resulting in metalloimmunotherapy. Furthermore, the immunostimulant OMVs played a crucial role in promoting the infiltration of activated CD8+T cells into the solid tumor. Overall, the nanoreactor offers a robust platform for solid tumor treatment, highlighting the significant potential of combining relief from tumor hypoxia and immune stimulation for metalloimmunotherapy. STATEMENT OF SIGNIFICANCE: A tailor-made nanoreactor was fabricated by enclosing bacterial-derived outer membrane vesicles (OMVs) onto MnO2 nanoenzyme and loading with immunogenic cell death inducer oxaliplatin (OxA) for tumor metalloimmunotherapy. The nanoreactor possesses intrinsic catalase-like activity within the tumor microenvironment, which effectively enabled a prolonged oxygen supply by catalyzing the conversion of endogenous H2O2 into O2, thereby alleviating tumor hypoxia and expediting OxA release. Furthermore, the TME-responsive release of nutritional Mn2+ sensitized the cGAS-STING pathway and collaborated with OxA-induced immunogenic cell death (ICD). Combing with immunostimulatory OMVs enhances the uptake of nanoreactors by DCs and promotes the infiltration of activated CD8+T cells. This nanoreactor offers a robust platform for solid tumor treatment, highlighting the significant potential of combining relief from tumor hypoxia and immune stimulation for metalloimmunotherapy.


Subject(s)
Immunotherapy , Tumor Microenvironment , Animals , Immunotherapy/methods , Mice , Tumor Microenvironment/drug effects , Cell Line, Tumor , Tumor Hypoxia/drug effects , Manganese Compounds/chemistry , Manganese Compounds/pharmacology , Oxaliplatin/pharmacology , Oxaliplatin/chemistry , Oxides/chemistry , Oxides/pharmacology , Manganese/chemistry , Manganese/pharmacology , Humans , Female , Neoplasms/therapy , Neoplasms/pathology , Neoplasms/immunology , Neoplasms/drug therapy , Dendritic Cells/drug effects , Dendritic Cells/metabolism , Dendritic Cells/immunology , Mice, Inbred C57BL
4.
J Anim Sci ; 1022024 Jan 03.
Article in English | MEDLINE | ID: mdl-38795007

ABSTRACT

The present study sought to assess the effects of manganese complexes with lysine and glutamic acid (Mn-LG) as manganese (Mn) sources on growth performance, trace element deposition, antioxidant capacity, and metacarpal strength in weaned piglets. The study involved 288 healthy Duroc × Landrace × Yorkshire piglets that were weaned at 25 to 28 d of age and weighed 8.66 ±â€…0.96 kg. These piglets were randomly divided into six groups: a control group (Mn-LG-0, receiving a basal diet without Mn supplementation), a Mn sulfate group (basal diet supplemented with 40 mg·kg-1 diet of Mn, Mn-S-40 group), and four Mn-LG groups (Mn-LG-20, Mn-LG-40, Mn-LG-60, Mn-LG-80, supplemented with 20, 40, 60, and 80 mg·kg-1 Mn from Mn-LG in the basal diet). Grouping began at weaning on the 0th day of the experiment. The corn-soybean-based basal diet during the early (days 0 to 14) and late (days 15 to 42) phases of the experiment contained 20.88 and 30.12 mg·kg-1 Mn, respectively. Blood samples were collected on days 14 and 42, and pigs were sacrificed for sample collection on day 42. The results indicated no significant differences in average daily gain, average daily feed intake, or feed-to-gain ratio among the groups (P > 0.05). The diarrhea rates of all Mn-LG groups and the Mn-S-40 group were significantly lower in the 0 to 14 d and during the entire experimental period than in the Mn-LG-0 group (P < 0.001). The Mn-LG-40 group exhibited a significant increase in liver Mn concentration and serum Mn superoxide dismutase (Mn-SOD) activity on day 42 (P < 0.01), as well as a significant decrease in fecal Mn concentration (P < 0.05), compared to those of the Mn-S-40 group. Significant differences (P < 0.05) were detected in the serum, liver, and fecal Mn concentrations, as well as in the serum and liver Mn-SOD activity, across the different Mn-LG groups. The serum and fecal Mn concentrations and serum Mn-SOD activity increased linearly or quadratically (P < 0.01) with increasing Mn-LG supplementation. No significant differences (P > 0.05) were found in kidney, heart, or metacarpal bone Mn concentrations or in bone strength indices. In summary, compared with the Mn-LG-0 diet, dietary supplementation with Mn-LG enhanced serum Mn deposition and Mn-SOD activity and decreased the incidence of diarrhea. Additionally, the fecal Mn concentration was lower in the Mn-LG group than in the inorganic group at equivalent dosages.


This research explored the effects of a manganese complex containing lysine and glutamic acid (Mn-LG) on various health parameters in weaned piglets. Utilizing samples of 288 piglets, the study investigated how Mn-LG supplementation influences growth performance, Mn deposition and emission, antioxidant capacity, and metacarpal strength. Key findings include an increase in serum Mn levels and Mn superoxide dismutase (Mn-SOD) activity, a reduction in diarrhea incidence, and no significant effects in bone strength indices in piglets receiving Mn-LG. Additionally, the fecal Mn concentration was notably lower in the Mn-LG group than in the group receiving inorganic Mn at equivalent dosages.


Subject(s)
Animal Feed , Antioxidants , Diet , Dietary Supplements , Glutamic Acid , Lysine , Manganese , Animals , Lysine/pharmacology , Lysine/administration & dosage , Lysine/metabolism , Animal Feed/analysis , Manganese/pharmacology , Manganese/administration & dosage , Manganese/metabolism , Diet/veterinary , Antioxidants/metabolism , Antioxidants/pharmacology , Dietary Supplements/analysis , Swine/growth & development , Glutamic Acid/pharmacology , Glutamic Acid/metabolism , Male , Female , Animal Nutritional Physiological Phenomena , Weaning , Random Allocation , Metacarpal Bones/metabolism , Metacarpal Bones/drug effects
5.
J Am Chem Soc ; 146(22): 15251-15263, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38780071

ABSTRACT

Glioblastoma (GBM) poses a significant therapeutic challenge due to its invasive nature and limited drug penetration through the blood-brain barrier (BBB). In response, here we present an innovative biomimetic approach involving the development of genetically engineered exosome nanocatalysts (Mn@Bi2Se3@RGE-Exos) for efficient GBM therapy via improving the BBB penetration and enzyme-like catalytic activities. Interestingly, a photothermally activatable multiple enzyme-like reactivity is observed in such a nanosystem. Upon NIR-II light irradiation, Mn@Bi2Se3@RGE-Exos are capable of converting hydrogen peroxide into hydroxyl radicals, oxygen, and superoxide radicals, providing a peroxidase (POD), oxidase (OXD), and catalase (CAT)-like nanocatalytic cascade. This consequently leads to strong oxidative stresses to damage GBM cells. In vitro, in vivo, and proteomic analysis further reveal the potential of Mn@Bi2Se3@RGE-Exos for the disruption of cellular homeostasis, enhancement of immunological response, and the induction of cancer cell ferroptosis, showcasing a great promise in anticancer efficacy against GBM with a favorable biosafety profile. Overall, the success of this study provides a feasible strategy for future design and clinical study of stimuli-responsive nanocatalytic medicine, especially in the context of challenging brain cancers like GBM.


Subject(s)
Exosomes , Glioblastoma , Infrared Rays , Phototherapy , Glioblastoma/drug therapy , Glioblastoma/therapy , Humans , Exosomes/chemistry , Exosomes/metabolism , Animals , Phototherapy/methods , Mice , Catalysis , Cell Line, Tumor , Brain Neoplasms/drug therapy , Brain Neoplasms/therapy , Brain Neoplasms/pathology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Manganese/chemistry , Manganese/pharmacology , Blood-Brain Barrier/metabolism
6.
ACS Nano ; 18(20): 12830-12844, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38709246

ABSTRACT

The immunosuppressive microenvironment of cervical cancer significantly hampers the effectiveness of immunotherapy. Herein, PEGylated manganese-doped calcium sulfide nanoparticles (MCSP) were developed to effectively enhance the antitumor immune response of the cervical cancer through gas-amplified metalloimmunotherapy with dual activation of pyroptosis and STING pathway. The bioactive MCSP exhibited the ability to rapidly release Ca2+, Mn2+, and H2S in response to the tumor microenvironment. H2S disrupted the calcium buffer system of cancer cells by interfering with the oxidative phosphorylation pathway, leading to calcium overload-triggered pyroptosis. On the other hand, H2S-mediated mitochondrial dysfunction further promoted the release of mitochondrial DNA (mtDNA), enhancing the activation effect of Mn2+ on the cGAS-STING signaling axis and thereby activating immunosuppressed dendritic cells. The released H2S acted as an important synergist between Mn2+ and Ca2+ by modulating dual signaling mechanisms to bridge innate and adaptive immune responses. The combination of MCSP NPs and PD-1 immunotherapy achieved synergistic antitumor effects and effectively inhibited tumor growth. This study reveals the potential collaboration between H2S gas therapy and metalloimmunotherapy and provides an idea for the design of nanoimmunomodulators for rational regulation of the immunosuppressive tumor microenvironment.


Subject(s)
Immunotherapy , Membrane Proteins , Pyroptosis , Tumor Microenvironment , Uterine Cervical Neoplasms , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Uterine Cervical Neoplasms/immunology , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/metabolism , Uterine Cervical Neoplasms/therapy , Female , Humans , Mice , Animals , Pyroptosis/drug effects , Membrane Proteins/metabolism , Manganese/chemistry , Manganese/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Nanoparticles/chemistry , Signal Transduction/drug effects , Cell Proliferation/drug effects , Calcium/metabolism , Mice, Inbred BALB C , Drug Screening Assays, Antitumor
7.
Bioresour Technol ; 402: 130794, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703966

ABSTRACT

Carbon deficits in inflow frequently lead to inefficient nitrogen removal in constructed wetlands (CWs) treating tailwater. Solid carbon sources, commonly employed to enhance denitrification in CWs, increase carbon emissions. In this study, MnO2 was incorporated into polycaprolactone substrates within CWs, significantly enhancing NH4+-N and NO3--N removal efficiencies by 48.26-59.78 % and 96.84-137.23 %, respectively. These improvements were attributed to enriched nitrogen-removal-related enzymes and increased plant absorption. Under high nitrogen loads (9.55 ± 0.34 g/m3/d), emissions of greenhouse gases (CO2, CH4, and N2O) decreased by 147.23-202.51 %, 14.53-86.76 %, and 63.36-87.36 %, respectively. N2O emissions were reduced through bolstered microbial nitrogen removal pathways by polycaprolactone and MnO2. CH4 accumulation was mitigated by the increased methanotrophs and dampened methanogenesis, modulated by manganese. Additionally, manganese-induced increases in photosynthetic pigment contents (21.28-64.65 %) fostered CO2 sequestration through plant photosynthesis. This research provides innovative perspectives on enhancing nitrogen removal and reducing greenhouse gas emissions in constructed wetlands with polymeric substrates.


Subject(s)
Carbon , Methane , Nitrogen , Wetlands , Nitrogen/metabolism , Carbon/metabolism , Methane/metabolism , Polyesters/metabolism , Polyesters/chemistry , Manganese/pharmacology , Plants/metabolism , Denitrification , Nitrous Oxide/metabolism , Carbon Dioxide/metabolism , Biodegradation, Environmental , Photosynthesis
8.
J Mater Chem B ; 12(17): 4097-4117, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38587869

ABSTRACT

Single phototherapy and immunotherapy have individually made great achievements in tumor treatment. However, monotherapy has difficulty in balancing accuracy and efficiency. Combining phototherapy with immunotherapy can realize the growth inhibition of distal metastatic tumors and enable the remote monitoring of tumor treatment. The development of nanomaterials with photo-responsiveness and anti-tumor immunity activation ability is crucial for achieving photo-immunotherapy. As immune adjuvants, photosensitizers and photothermal agents, manganese-based nanoparticles (Mn-based NPs) have become a research hotspot owing to their multiple ways of anti-tumor immunity regulation, photothermal conversion and multimodal imaging. However, systematic studies on the synergistic photo-immunotherapy applications of Mn-based NPs are still limited; especially, the green synthesis and mechanism of Mn-based NPs applied in immunotherapy are rarely comprehensively discussed. In this review, the synthesis strategies and function of Mn-based NPs in immunotherapy are first introduced. Next, the different mechanisms and leading applications of Mn-based NPs in immunotherapy are reviewed. In addition, the advantages of Mn-based NPs in synergistic photo-immunotherapy are highlighted. Finally, the challenges and research focus of Mn-based NPs in combination therapy are discussed, which might provide guidance for future personalized cancer therapy.


Subject(s)
Immunotherapy , Manganese , Humans , Manganese/chemistry , Manganese/pharmacology , Immunotherapy/methods , Phototherapy/methods , Green Chemistry Technology , Neoplasms/therapy , Neoplasms/drug therapy , Animals , Nanostructures/chemistry , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Photosensitizing Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Particle Size
9.
Acta Biomater ; 179: 243-255, 2024 04 15.
Article in English | MEDLINE | ID: mdl-38458511

ABSTRACT

Oncolytic viral therapy (OVT) is a novel anti-tumor immunotherapy approach, specifically replicating within tumor cells. Currently, oncolytic viruses are mainly administered by intratumoral injection. However, achieving good results for distant metastatic tumors is challenging. In this study, a multifunctional oncolytic adenovirus, OA@CuMnCs, was developed using bimetallic ions copper and manganese. These metal cations form a biomineralized coating on the virus's surface, reducing immune clearance. It is known that viruses upregulate the expression of PD-L1. Copper ions in OA@CuMnCs can decrease the PD-L1 expression of tumor cells, thereby promoting immune cell-related factor release. This process involves antigen presentation and the combination of immature dendritic cells, transforming them into mature dendritic cells. It changes "cold" tumors into "hot" tumors, further inducing immunogenic cell death. While oncolytic virus replication requires oxygen, manganese ions in OA@CuMnCs can react with endogenous hydrogen peroxide. This reaction produces oxygen, enhancing the virus's replication ability and the tumor lysis effect. Thus, this multifunctionally coated OA@CuMnCs demonstrates potent amplification in immunotherapy efficacy, and shows great potential for further clinical OVT. STATEMENT OF SIGNIFICANCE: Oncolytic virus therapy (OVs) is a new anti-tumor immunotherapy method that can specifically replicate in tumor cells. Although the oncolytic virus can achieve a therapeutic effect on some non-metastatic tumors through direct intratumoral injection, there are still three major defects in the treatment of metastatic tumors: immune response, hypoxia effect, and administration route. Various studies have shown that the immune response in vivo can be overcome by modifying or wrapping the surface protein of the oncolytic virus. In this paper, a multifunctional coating of copper and manganese was prepared by combining the advantages of copper and manganese ions. The coating has a simple preparation method and mild conditions, and can effectively enhance tumor immunotherapy.


Subject(s)
Adenoviridae , Colorectal Neoplasms , Copper , Immunotherapy , Manganese , Oncolytic Virotherapy , Oncolytic Viruses , Copper/chemistry , Copper/pharmacology , Manganese/chemistry , Manganese/pharmacology , Immunotherapy/methods , Animals , Colorectal Neoplasms/therapy , Colorectal Neoplasms/pathology , Oncolytic Virotherapy/methods , Humans , Cell Line, Tumor , Mice , Mice, Inbred BALB C , Female
10.
ACS Appl Bio Mater ; 7(3): 1862-1877, 2024 03 18.
Article in English | MEDLINE | ID: mdl-38450575

ABSTRACT

Elevated levels of reactive oxygen species (ROS) have demonstrated efficacy in eliminating tumor cells by modifying the tumor microenvironment and inducing the polarization of tumor-associated macrophages (TAMs). Nevertheless, the transient nature and limited diffusion distance inherent in ROS present significant challenges in cancer treatment. In response to these limitations, we have developed a nanoparticle (MnClPc-HSA@GOx) that not only inhibits tumor energy metabolism but also facilitates the transition of TAMs from the M2 type (anti-inflammatory type) to the M1 type (proinflammatory type). MnClPc-HSA@GOx comprises a manganese phthalocyanine complex (MnClPc) enveloped in human serum albumin (HSA), with glucose oxidase (GOx) loaded onto MnClPc@HSA nanoparticles. GOx was employed to catalyze the decomposition of glucose to produce H2O2 and gluconic acid. Additionally, in the presence of MnClPc, it catalyzes the conversion of H2O2 into •O2- and 1O2. Results indicate that the nanoparticle effectively impedes the glucose supply to tumor cells and suppresses their energy metabolism. Simultaneously, the ROS-mediated polarization of TAMs induces a shift from M2 to M1 macrophages, resulting in a potent inhibitory effect on tumors. This dual-action strategy holds promising clinical inhibition applications in the treatment of cancer.


Subject(s)
Isoindoles , Nanoparticles , Neoplasms , Humans , Manganese/pharmacology , Glucose Oxidase/metabolism , Reactive Oxygen Species/metabolism , Hydrogen Peroxide/metabolism , Neoplasms/metabolism , Macrophages , Oxygen/metabolism , Energy Metabolism , Glucose , Tumor Microenvironment
11.
ACS Appl Mater Interfaces ; 16(14): 17129-17144, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38533538

ABSTRACT

Immune-cell-derived membranes have garnered significant attention as innovative delivery modalities in cancer immunotherapy for their intrinsic immune-modulating functionalities and superior biocompatibilities. Integrating additional parental cell membranes or synthetic lipid vesicles into cellular vesicles can further potentiate their capacities to perform combinatorial pharmacological activities in activating antitumor immunity, thus providing insights into the potential of hybrid cellular vesicles as versatile delivery vehicles for cancer immunotherapy. Here, we have developed a macrophage-membrane-derived hybrid vesicle that has the dual functions of transporting immunotherapeutic drugs and shaping the polarization of tumor-associated macrophages for cancer immunotherapy. The platform combines M1 macrophage-membrane-derived vesicles with CXCR4-binding-peptide-conjugated liposomes loaded with manganese and doxorubicin. The hybrid nanovesicles exhibited remarkable macrophage-targeting capacity through the CXCR4-binding peptide, resulting in enhanced macrophage polarization to the antitumoral M1 phenotype characterized by proinflammatory cytokine release. The manganese/doxorubicin-loaded hybrid vesicles in the CXCR4-expressing tumor cells evoked potent cancer cytotoxicity, immunogenic cell death of tumor cells, and STING activation. Moreover, cotreatment with manganese and doxorubicin promoted dendritic cell maturation, enabling effective tumor growth inhibition. In murine models of CT26 colon carcinoma and 4T1 breast cancer, intravenous administration of the manganese/doxorubicin-loaded hybrid vesicles elicited robust tumor-suppressing activity at a low dosage without adverse systemic effects. Local administration of hybrid nanovesicles also induced an abscessive effect in a bilateral 4T1 tumor model. This study demonstrates a promising biomimetic manganese/doxorubicin-based hybrid nanovesicle platform for effective cancer immunotherapy tailored to the tumor microenvironment, which may offer an innovative approach to combinatorial immunotherapy.


Subject(s)
Breast Neoplasms , Neoplasms , Humans , Animals , Mice , Female , Manganese/pharmacology , Biomimetics , Doxorubicin/therapeutic use , Macrophages/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Neoplasms/drug therapy , Neoplasms/metabolism , Immunotherapy/methods , Peptides/pharmacology , Tumor Microenvironment , Cell Line, Tumor , Receptors, CXCR4/metabolism
12.
J Anim Sci ; 1022024 Jan 03.
Article in English | MEDLINE | ID: mdl-38430558

ABSTRACT

To investigate effects of inorganic or complexed trace mineral source (zinc, copper, manganese, and cobalt) on receiving period performance and morbidity, crossbred beef heifer calves (n = 287) arriving on three delivery dates were used in a 42-d receiving trial. Heifers were processed after arrival, stratified by day -1 body weights (BW) and allocated randomly to eight pens (11 to 13 heifers/pen, 24 pens total). Within truckload, pens were assigned randomly to dietary treatment (n = 12 pens/treatment). Heifers were housed on 0.42-ha grass paddocks, provided ad libitum bermudagrass hay and provided dietary treatments in grain supplements fed daily. Treatments consisted of supplemental zinc (360 mg/d), copper (125 mg/d), manganese (200 mg/d), and cobalt (12 mg/d) from complexed (Zinpro Availa 4, Zinpro Corp. Eden Prairie, MN) or inorganic sources (sulfates). Heifers were observed daily for clinical bovine respiratory disease (BRD). If presenting BRD symptoms and rectal temperature ≥ 40 °C, heifers were deemed morbid and treated with antibiotics. Six heifers/pen were bled to determine serum haptoglobin concentrations on days 0, 14, and 28. Liver biopsies were taken on day 5 ±â€…2 and 43 ±â€…1 from three calves selected randomly from each pen for mineral status comparisons. Statistical analyses were performed using the MIXED, GLIMMIX, and repeated measures procedures of SAS 9.4 with truckload as a random effect and pen within truckload specified as subject. There tended to be a treatment by day interaction for BW (P = 0.07). Heifer BW did not differ on day 0 (P = 0.82) and day 14 (P = 0.36), but heifers fed complexed trace minerals had greater BW on day 28 (P = 0.04) and day 42 (P = 0.05). Overall average daily gains were greater for heifers fed complexed trace minerals (P = 0.05; 0.78 vs. 0.70 kg, SE = 0.03). Heifers supplemented with inorganic trace minerals had greater BRD incidence (P = 0.03; 58 vs. 46%, SE = 3.6). Haptoglobin concentrations decreased throughout the trial (P < 0.001), and heifers fed complexed trace minerals tended to have a decrease in haptoglobin concentrations (P = 0.07). The source of trace mineral supplementation had no effect (P ≥ 0.20) on liver mineral concentrations and there were no treatment × day interactions (P ≥ 0.35). In conclusion, supplementing diets for the first 42 d after arrival with complexed trace mineral sources improved heifer performance as compared to heifers supplemented with inorganic trace minerals.


Issues associated with health and management of newly received cattle continue to pose significant animal welfare and economic challenges for the beef industry. Diagnosis of bovine respiratory disease, accompanied with poor growth performance, can be addressed by nutritional intervention in receiving cattle. Trace mineral inclusion in receiving rations is vital to calf performance. There are numerous sources of trace mineral supplements that exist commercially for cattle and their effects on immune function, growth, and performance measures were evaluated. Organic trace mineral supplements are being used in replacement of inorganic salts due to potentially greater bioavailability and functionality. An organic source that is commonly used are amino acid complexes. Replacing inorganic sources with complexed sources of trace minerals (zinc, copper, manganese, and cobalt) improved growth performance and decreased sickness during the 42-d receiving study.


Subject(s)
Trace Elements , Cattle , Animals , Female , Trace Elements/pharmacology , Manganese/pharmacology , Copper/pharmacology , Haptoglobins/analysis , Dietary Supplements , Minerals/pharmacology , Zinc/pharmacology , Cobalt/pharmacology , Diet/veterinary , Body Weight , Animal Feed/analysis
13.
J Agric Food Chem ; 72(14): 7564-7585, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38536968

ABSTRACT

Manganese (Mn) is an important microelement for the mineral nutrition of plants, but it is not effectively absorbed from the soil and mineral salts added thereto and can also be toxic in high concentrations. Mn nanoparticles (NPs) are less toxic, more effective, and economical than Mn salts due to their nanosize. This article critically reviews the current publications on Mn NPs, focusing on their effects on plant health, growth, and stress tolerance, and explaining possible mechanisms of their effects. This review also provides basic information and examples of chemical, physical, and ecological ("green") methods for the synthesis of Mn NPs. It has been shown that the protective effect of Mn NPs is associated with their antioxidant activity, activation of systemic acquired resistance (SAR), and pronounced antimicrobial activity against phytopathogens. In conclusion, Mn NPs are promising agents for agriculture, but their effects on gene expression and plant microbiome require further research.


Subject(s)
Metal Nanoparticles , Nanoparticles , Manganese/pharmacology , Manganese/metabolism , Chemistry, Agricultural , Salts , Minerals
14.
J Nanobiotechnology ; 22(1): 103, 2024 Mar 11.
Article in English | MEDLINE | ID: mdl-38468261

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a prevalent inflammatory autoimmune disease characterised by persistent inflammation and joint damage with elevated levels of reactive oxygen species (ROS). Current treatment modalities for RA have significant limitations, including poor bioavailability, severe side effects, and inadequate targeting of inflamed joints. Herein, we synthesised cerium/manganese oxide nanoparticles (NPs) as efficient drug carriers with antioxidant and catalytic-like functions that can eliminate ROS to facilitate the polarization of macrophages phenotype from M1 to M2 and alleviate inflammation. Methotrexate (MTX), a first-line RA medication, was loaded into the NPs, which were further modified with bovine serum albumin (BSA) and integrated into dissolving hyaluronic acid-based microneedles (MNs) for transdermal delivery. RESULT: This innovative approach significantly enhanced drug delivery efficiency, reduced RA inflammation, and successfully modulated macrophage polarization toward an anti-inflammatory phenotype. CONCLUSION: This research not only presents a promising drug delivery strategy for RA but also contributes broadly to the field of immune disease treatment by offering an advanced approach for macrophage phenotypic reprogramming.


Subject(s)
Arthritis, Rheumatoid , Cerium , Manganese Compounds , Nanoparticles , Oxides , Humans , Manganese/pharmacology , Reactive Oxygen Species/pharmacology , Arthritis, Rheumatoid/drug therapy , Macrophages , Inflammation , Cerium/pharmacology
15.
Animal ; 18(4): 101126, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38552601

ABSTRACT

Poor eggshell quality of eggs laid by aged laying hens is the major problem affecting the length of the rearing period in the laying hen industry. Trace elements are required and play vital roles in the eggshell quality of laying hens. Appropriate dose of organic microelements is environmentally friendly and sufficient to satisfy the needs of hens because of their greater bioavailability and lower excretion than inorganic forms. The aim of this experiment was to investigate the effects of manganese (Mn) glycine (MG) on eggshell quality, elemental deposition, and eggshell ultrastructure in aged laying hens. A total of 720 Hy-Line Brown hens 70 weeks old were assigned equally to four groups with six replicates of 30 birds each. The hens were fed basal diets (without Mn supplementation) supplemented with 120 mg/kg of Mn from manganese sulfate monohydrate (MSM), or 40, 80, or 120 mg/kg Mn from MG for 12 weeks. Dietary supplementation with 80 mg/kg Mn from MG resulted in the greatest eggshell strength after 6 weeks of treatment (P = 0.047), and in greater eggshell strength than observed in the MSM control after 12 weeks of treatment (P = 0.025). After 12 weeks of treatment, the eggs of hens in the MG groups showed lower mammillary layer thickness in the blunt end, equator, and acute end than observed in the MSM control group (P < 0.001). With the exception of the blunt ends of eggs from hens in the 120 mg/kg MG group, the eggs of hens in the MG groups, compared with the MSM control group, exhibited a lower mammillary layer ratio, and greater palisade layer ratio and effective layer ratio in the blunt end, equator, and acute end (P < 0.001). Dietary supplementation with 80 mg/kg Mn from MG, compared with the MSM control and 40 and 120 mg/kg MG, resulted in the greatest palisade layer thickness and effective layer thickness, and the lowest mammillary layer thickness in the equator (P < 0.001, P = 0.001, P < 0.001, respectively). Furthermore, supplementation with 80 mg/kg Mn from MG exhibited the greatest ratio of the palisade layer and effective layer, and the lowest mammillary layer ratio in the blunt end and equator (all P < 0.001). The Mn content of eggshells in hens-fed diets supplemented with 80 and 120 mg/kg Mn from MG was greater than that in the MSM control and 40 mg/kg MG groups (P = 0.035). Dietary supplementation with 80 or 120 mg/kg Mn from MG resulted in greater tibia Mn content than observed in the 40 mg/kg MG group (P = 0.019), and greater yolk Mn content than observed in the 40 mg/kg MG and MSM control groups (P = 0.018). In conclusion, dietary supplementation with 80 mg/kg Mn from MG, compared with the MSM control (120 mg/kg Mn), may increase the deposition efficiency of Mn, alter eggshell elemental composition, improve eggshell ultrastructure, and enhance eggshell strength in aged laying hens.


Subject(s)
Fabaceae , Manganese , Animals , Female , Manganese/pharmacology , Egg Shell , Chickens , Ovum , Dietary Supplements , Diet/veterinary , Animal Feed/analysis
16.
Anticancer Res ; 44(3): 953-962, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38423638

ABSTRACT

BACKGROUND/AIM: Treatment of castration-resistant prostate cancer with docetaxel (DOC) often leads to resistance. In this study, we investigated whether manganese (Mn) has the potential to enhance treatment when combined with DOC. MATERIALS AND METHODS: PC3 cells were exposed to DOC or Mn individually and in combination and cell viability was analysed in a dose- and time-dependent manner. Cell toxicity, cell cycle analysis and apoptotic protein levels were determined after 48 h of treatment. RESULTS: Mn in combination with different concentrations of DOC significantly enhanced the inhibitory effect on cell viability. Although the lowest dose did not cause mitotic arrest, DOC increased toxicity, which was reduced when combined with Mn. Protein analyses indicated that Mn compensates for the suppression of death receptors when combined with a low concentration of DOC and induced non-apoptotic pathways when combined with a higher concentration. CONCLUSION: Combining DOC and Mn may allow for a reduction in DOC concentration with the potential to reduce side effects.


Subject(s)
Antineoplastic Agents , Prostatic Neoplasms , Male , Humans , Docetaxel/pharmacology , Docetaxel/therapeutic use , Manganese/pharmacology , Apoptosis , Cell Line, Tumor , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
17.
Future Microbiol ; 19: 385-395, 2024 03.
Article in English | MEDLINE | ID: mdl-38381028

ABSTRACT

Background: New chemotherapeutics are urgently required to treat Candida infections caused by drug-resistant strains. Methods: The effects of 16 1,10-phenanthroline (phen)/1,10-phenanthroline-5,6-dione/dicarboxylate complexed with Mn(II), Cu(II) and Ag(I) were evaluated against ten different Candida species. Results: Proliferation of Candida albicans, Candida dubliniensis, Candida famata, Candida glabrata, Candida guilliermondii, Candida kefyr, Candida krusei, Candida lusitaniae, Candida parapsilosis and Candida tropicalis was inhibited by three of six Cu(II) (MICs 1.52-21.55 µM), three of three Ag(I) (MICs 0.11-12.74 µM) and seven of seven Mn(II) (MICs 0.40-38.06 µM) complexes. Among these [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2].4H2O, where oda = octanedioic acid, exhibited effective growth inhibition (MICs 0.4-3.25 µM), favorable activity indexes, low toxicity against Vero cells and good/excellent selectivity indexes (46.88-375). Conclusion: [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2].4H2O represents a promising chemotherapeutic option for emerging, medically relevant and drug-resistant Candida species.


Candida species are widespread fungi that can cause a variety of infections in humans, and some of them exhibit resistance profile to existing antifungal drugs. Consequently, it is imperative to discover novel treatments for these clinically relevant human infections. Complexes are chemical compounds containing metal ion components that are well-known for their antimicrobial properties, including antifungal activity. In the present study, we investigated the effects of 16 novel complexes against ten medically relevant Candida species, including some strains resistant to commonly used clinical antifungals. Our findings revealed that all complexes containing manganese and silver metals effectively inhibited the growth of all Candida species tested, albeit to varying extents. Some of these complexes exhibited superior antifungal activity and lower toxicity to mammalian cells compared to traditional antifungals, such as fluconazole. In conclusion, these new complexes hold promise as a potential novel approach for treating fungal infections, especially those caused by drug-resistant Candida strains.


Subject(s)
Antifungal Agents , Copper , Phenanthrolines , Animals , Chlorocebus aethiops , Copper/pharmacology , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Silver/pharmacology , Manganese/pharmacology , Vero Cells , Candida , Candida albicans , Microbial Sensitivity Tests , Drug Resistance, Fungal
18.
Int J Biol Macromol ; 262(Pt 1): 130019, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38331077

ABSTRACT

As an essential trace element for plant growth and development, manganese plays a crucial role in the uptake of the heavy metal cadmium by rice (Oryza sativa L.). In this study, we developed a novel slow-release manganese fertilizer named Mn@LNS-EL. Initially, lignin nanoparticles were derived from sodium lignosulfonate, and a one-step emulsification strategy was employed to prepare a water-in-oil-in-water (W/O/W) Pickering double emulsions. These double emulsions served as the template for interfacial polymerization of lignin nanoparticles and epichlorohydrin, resulting in the formation of microcapsule wall materials. Subsequently, manganese fertilizer (MnSO4) was successfully encapsulated within the microcapsules. Hydroponic experiments were conducted to investigate the effects of Mn@LNS-EL on rice growth and the cadmium and manganese contents in the roots and shoots of rice under cadmium stress conditions. The results revealed that the treatment with Mn@LNS-EL markedly alleviated the inhibitory effects of cadmium on rice growth, leading to notably lower cadmium levels in the rice roots and shoots compared to the specimens treated without manganese fertilizer. Specifically, there was a reduction of 37.9 % in the root cadmium content and a 17.1 % decrease in the shoot cadmium content. In conclusion, this study presents an innovative approach for the high-value utilization of lignin through effective encapsulation and slow-release mechanisms of trace-element fertilizers while offering a promising strategy for efficiently remediating cadmium pollution in rice.


Subject(s)
Oryza , Soil Pollutants , Trace Elements , Manganese/pharmacology , Lignin/pharmacology , Fertilizers/analysis , Cadmium/pharmacology , Water/pharmacology , Soil Pollutants/pharmacology , Plant Roots/chemistry , Soil
19.
Plant Physiol Biochem ; 207: 108428, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38364633

ABSTRACT

Manganese (Mn) is one of the essential elements for plant growth and is involved in the process of photosynthesis and seed germination. Herein, we applied two Mn-based nanoparticles, MnO2 and Mn3O4, to the soil to investigate their effects on radish growth, antioxidant system, and nutrients. The radish plant height after treatment with 10 mg/kg of MnO2 and Mn3O4 NPs were increased, compare to the control. In radish's shoot, MnO2 NPs at high concentrations (100 mg/kg) increased MDA activity by 58 % compared to the control group, while exposure to Mn3O4 NPs at the same concentration decreased MDA activity by 14 %. The nutrient content of radishes, such as soluble sugar and vitamin C, was improved. Moreover, single particle inductively coupled plasma mass spectrometry (SP ICP-MS) was used to understand the patterns of migration of Mn-based NPs in radish and subsequent impact on nutrients. We found that Mn-based NPs accumulated mainly in the roots of radish. Interestingly, the accumulation characteristics of MnO2 NPs and Mn3O4 NPs were different. MnO2 NPs accumulated more in radish leaves than in fruits, while the accumulation of Mn3O4 NPs gradually decreased from roots to leaves. Finally, we determined the mineral element content of the leaves, fruits, and roots of radish, and found that the uptake of main metallic mineral elements (e.g. Cu, Fe, Mg, Zn, Na, K) was inhibited by the application of Mn-based NPs. These findings underscore the importance of considering species and multifaceted impacts of Mn-based NPs as nanofertilizers for their wide application in agriculture.


Subject(s)
Nanoparticles , Raphanus , Raphanus/chemistry , Manganese/pharmacology , Manganese Compounds/pharmacology , Oxides/pharmacology , Minerals/pharmacology
20.
Chemosphere ; 351: 141140, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38190943

ABSTRACT

Oxides of silicon (Si), manganese (Mn), and zinc (Zn) have been used as soil amendments to reduce As mobility and uptake in paddy soil systems. However, these amendments are hypothesized to be affected differently depending on the soil pH and their effect on As speciation in rice paddy systems is not fully understood. Herein, we used a microcosm experiment to investigate the effects of natural Si-rich fly ash and synthetic Mn and Zn oxides on the temporal development of porewater chemistry, including aqueous As speciation (As(III), As(V), MMA, DMA, and DMMTA) and solid-phase As solubility, in a naturally calcareous soil with or without soil acidification (with sulfuric acid) during 28 days of flooding and subsequent 14 days of drainage. We found that soil acidification to pH 4.5 considerably increased the solubility of Si, Fe, Mn, and Zn compared to the non-acidified soil. Additions of Mn and Zn oxides decreased the concentrations of dissolved arsenite and arsenate in the non-acidified soil whereas additions of Zn oxide and combined Si-Zn oxides increased them in the acidified soil. The Si-rich fly ash did not increase dissolved Si and As in the acidified and non-acidified soils. Dimethylated monothioarsenate (DMMTA) was mainly observed in the acidified soil during the later stage of soil flooding. The initial 28 days of soil flooding decreased the levels of soluble and exchangeable As and increased As associated with Mn oxides, whereas the subsequent 14 days of soil drainage reversed the trend. This study highlighted that soil acidification considerably controlled the solubilization of Ca and Fe, thus influencing the soil pH-Eh buffering capacity, the solubility of Si, Mn, and Zn oxides, and the mobility of different As species in carbonate-rich and acidic soils under redox fluctuations.


Subject(s)
Arsenic , Oryza , Soil Pollutants , Zinc Oxide , Arsenic/analysis , Manganese/pharmacology , Soil , Silicon/pharmacology , Coal Ash/pharmacology , Zinc Oxide/pharmacology , Oxides/pharmacology , Organic Chemicals/pharmacology , Zinc/pharmacology , Soil Pollutants/analysis
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