Evaluation of the biodistribution and preliminary safety profile of a novel brain-targeted manganese dioxide-based nanotheranostic system for Alzheimer's disease.

A novel brain-targeted and reactive oxygen species-activatable manganese dioxide containing nanoparticle system functionalized with anti-amyloid-ß antibody (named aAß-BTRA-NC) developed by our group has shown great promise as a highly selective magnetic resonance imaging (MRI) contrast agent for early detection and multitargeted disease-modifying treatment of Alzheimer's disease (AD). To further evaluate the suitability of the formulation for future clinical application, we investigated the safety, biodistribution, and pharmacokinetic profile of aAß-BTRA-NC in a transgenic TgCRND8 mouse AD model, wild type (WT) littermate, and CD-1 mice. Dose-ascending studies demonstrated that aAß-BTRA-NC was well-tolerated by the animals up to 300 µmol Mn/kg body weight [b.w.], 3 times the efficacious dose for early AD detection without apparent adverse effects; Histopathological, hematological, and biochemical analyses indicated that a single dose of aAß-BTRA-NC did not cause any toxicity in major organs. Immunotoxicity data showed that aAß-BTRA-NC was safer than commercially available gadolinium-based MRI contrast agents at an equivalent dose of 100 µmol/kg b.w. of metal ions. Intravenously administered aAß-BTRA-NC was taken up by main organs with the order of liver, kidneys, intestines, spleen, followed by other organs, and cleared after one day to one week post injection. Pharmacokinetic analysis indicated that the plasma concentration profile of aAß-BTRA-NC followed a 2-compartmental model with faster clearance in the AD mice than in the WT mice. The results suggest that aAß-BTRA-NC exhibits a strong safety profile as a nanotheranostic agent which warrants more robust preclinical development for future clinical applications.

Manganese dioxide nanoparticles provoke inflammatory damage in BV2 microglial cells via increasing reactive oxygen species to activate the p38 MAPK pathway.

With the widespread use of manganese dioxide nanoparticles (nano MnO2), health hazards have also emerged. The inflammatory damage of brain tissues could result from nano MnO2, in which the underlying mechanism is still unclear. During this study, we aimed to investigate the role of ROS-mediated p38 MAPK pathway in nano MnO2-induced inflammatory response in BV2 microglial cells. The inflammatory injury model was established by treating BV2 cells with 2.5, 5.0, and 10.0 µg/mL nano MnO2 suspensions for 12 h. Then, the reactive oxygen species (ROS) scavenger (20 nM N-acetylcysteine, NAC) and the p38 MAPK pathway inhibitor (10 µM SB203580) were used to clarify the role of ROS and the p38 MAPK pathway in nano MnO2-induced inflammatory lesions in BV2 cells. The results indicated that nano MnO2 enhanced the expression of pro-inflammatory cytokines IL-1ß and TNF-α, elevated intracellular ROS levels and activated the p38 MAPK pathway in BV2 cells. Controlling intracellular ROS levels with NAC inhibited p38 MAPK pathway activation and attenuated the inflammatory response induced by nano MnO2. Furthermore, inhibition of the p38 MAPK pathway with SB203580 led to a decrease in the production of inflammatory factors (IL-1ß and TNF-α) in BV2 cells. In summary, nano MnO2 can induce inflammatory damage by increasing intracellular ROS levels and further activating the p38 MAPK pathway in BV2 microglial cells.

Biocompatible and bioactivable terpolymer-lipid-MnO2 Nanoparticle-based MRI contrast agent for improving tumor detection and delineation.

Early and precise detection of solid tumor cancers is critical for improving therapeutic outcomes. In this regard, magnetic resonance imaging (MRI) has become a useful tool for tumor diagnosis and image-guided therapy. However, its effectiveness is limited by the shortcomings of clinically available gadolinium-based contrast agents (GBCAs), i.e. poor tumor penetration and retention, and safety concerns. Thus, we have developed a novel nanoparticulate contrast agent using a biocompatible terpolymer and lipids to encapsulate manganese dioxide nanoparticles (TPL-MDNP). The TPL-MDNP accumulated in tumor tissue and produced paramagnetic Mn2+ ions, enhancing T1-weight MRI contrast via the reaction with H2O2 rich in the acidic tumor microenvironment. Compared to the clinically used GBCA, Gadovist®1.0, TPL-MDNP generated stronger T1-weighted MR signals by over 2.0-fold at 30 % less of the recommended clinical dose with well-defined tumor delineation in preclinical orthotopic tumor models of brain, breast, prostate, and pancreas. Importantly, the MRI signals were retained for 60 min by TPL-MDNP, much longer than Gadovist®1.0. Biocompatibility of TPL-MDNP was evaluated and found to be safe up to 4-fold of the dose used for MRI. A robust large-scale manufacturing process was developed with batch-to-batch consistency. A lyophilization formulation was designed to maintain the nanostructure and storage stability of the new contrast agent.

Manganese Dioxide-Entrapping Dendrimers Co-Deliver Protein and Nucleotide for Magnetic Resonance Imaging-Guided Chemodynamic/Starvation/Immune Therapy of Tumors.

Development of a nanoscale drug delivery system that can simultaneously exert efficient tumor therapeutic efficacy while creating the desired antitumor immune responses is still challenging. Herein, we report the use of a manganese dioxide (MnO2)-entrapping dendrimer nanocarrier to codeliver glucose oxidase (GOx) and cyclic GMP-AMP (cGAMP), an agonist of the stimulator of interferon genes (STING) for improved tumor chemodynamic/starvation/immune therapy. Methoxy poly(ethylene glycol) (mPEG)- and phenylboronic acid (PBA)-modified generation 5 (G5) poly(amidoamine) dendrimers were first synthesized and then entrapped with MnO2 nanoparticles (NPs) to generate the hybrid MnO2@G5-mPEG-PBA (MGPP) NPs. The created MGPP NPs with an MnO2 core size of 2.8 nm display efficient glutathione depletion ability, and a favorable Mn2+ release profile under a tumor microenvironment mimetic condition to enable Fenton-like reaction and T1-weighted magnetic resonance (MR) imaging. We show that the MGPP-mediated GOx delivery facilitates enhanced chemodynamic/starvation therapy of cancer cells in vitro, and further codelivery of cGAMP can effectively trigger immunogenic cell death (ICD) to strongly promote the maturation of dendritic cells. In a bilateral mouse colorectal tumor model, the dendrimer delivery nanosystem elicits a potent antitumor performance with a strong abscopal effect, greatly improving the overall mouse survival rate. Importantly, the dendrimer-mediated codelivery not only allows the coordination of Mn2+ with GOx and cGAMP for respective chemodynamic/starvation-triggered ICD and augmented STING activation to boost systemic antitumor immune responses, but also enables T1-weighted tumor MR imaging, potentially serving as a promising nanoplatform for enhanced antitumor therapy with desired immune responses.

Phytic acid-modified manganese dioxide nanoparticles oligomer for magnetic resonance imaging and targeting therapy of osteosarcoma.

Osteosarcoma is the most common malignant tumor in the skeletal system with high mortality. Phytic acid (PA) is a natural compound extracted from plant seeds, which shows certain antitumor activity and good bone targeting ability. To develop a novel theranostics for magnetic resonance imaging (MRI) and targeting therapy of osteosarcoma, we employed PA to modify manganese dioxide nanoparticles (MnO2@PA NPs) for osteosarcoma treatment. The MnO2 NPs oligomer was formed by PA modification with uniformed size distribution and negative zeta potential. Fourier-transform infrared spectroscopy, X-ray diffraction, energy dispersive spectroscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis demonstrated that PA has been successfully modified on MnO2 NPs, and the structure of MnO2@PA NPs is amorphous. In vitro experiments demonstrated that MnO2@PA NPs oligomer can be efficiently internalized by tumor cell, and the internalized NPs can react with H2O2 under acid microenvironment to produce Mn2+ and O2. In vivo experiments demonstrated that MnO2@PA NPs oligomer can passively accumulate in tumor tissue, and the accumulated NPs can produce Mn2+ and O2 for MRI and targeting therapy of osteosarcoma. In conclusion, we prepared a novel bone-targeting nano theranostics for MRI and therapy of osteosarcoma.

Immunomodulatory activity of manganese dioxide nanoparticles: Promising for novel vaccines and immunotherapeutics.

Manganese (Mn), a nutrient inorganic trace element, is necessary for a variety of physiological processes of animal body due to their important roles in oxidative regulation effects and other aspects of activities. Moreover, manganese ion (Mn2+) has widely reported to be crucial for the regulations of different immunological responses, thus showing promising application as potential adjuvants and immunotherapeutics. Taking the advantages of Mn-based biological and immunological activities, Manganese dioxide nanoparticles (MnO2 NPs) are a new type of inorganic nanomaterials with numerous advantages, including simple preparation, low cost, environmental friendliness, low toxicity, biodegradable metabolism and high bioavailability. MnO2 NPs, as a kind of drug carrier, have also shown the ability to catalyze hydrogen peroxide (H2O2) to produce oxygen (O2) under acidic conditions, which can enhance the efficacy of radiotherapy, chemotherapy and other therapeutics for tumor treatment by remodeling the tumor microenvironment. More importantly, MnO2 NPs also play important roles in immune regulations both in innate and adaptive immunity. In this review, we summarize the biological activities of Manganese, followed by the introduction for the biological and medical functions and mechanisms of MnO2 NPs. What's more, we emphatically discussed the immunological regulation effects and mechanisms of MnO2 NPs, as well as their potentials to serve as adjuvants and immunomodulators, which might benefit the development of novel vaccines and immunotherapies for more effective disease control.

Perfluorooctyl bromide nanoemulsions holding MnO2 nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death.

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO2 nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8+ and CD4+ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.

Tumour microenvironment-responsive nanoplatform based on biodegradable liposome-coated hollow MnO2 for synergistically enhanced chemotherapy and photodynamic therapy.

BACKGROUND: Existing therapeutic efficacy of chemotherapy and photodynamic therapy (PDT) is always affected by some resistance factors from tumour environment (TME), such as hypoxia and the antioxidant defense system. PURPOSE: This study aims at developing a cascaded intelligent multifunctional nanoplatforms to modulate the TME resistance for synergistically enhanced chemo- and photodynamic therapies. METHODS: In this study, we synthesised hollow manganese dioxide nanoparticles (HMDNs) loaded with the hydrophilic chemotherapeutic drug (acriflavine, ACF) and the hydrophobic photosensitizer (chlorine6, Ce6), which was further encapsulated by pH-sensitive liposome to form core-shell nanocomposite, with surface modified with arginine-glycine-aspartic acid (RGD) peptide to achieve tumour targeting. RESULTS: After uptake by tumour cells, the liposome shell was rapidly degraded by the low pH, and the inner core could be released from the liposome. Then, the released HMDNs/ACF/Ce6 would be dissociated by low pH and high levels of intracellular GSH within TME to release encapsulated drugs, thereby resulting in synergistic effects of chemotherapy and PDT. Meanwhile, the released ACF could bind with HIF-1a and then inhibit the expression levels of HIF-1's downstream signalling molecules P-gp and VEGF, which could further strengthen the antitumor effects. As a result, HMDNs/ACF/Ce6@Lipo-RGD NPs with laser irradiation exhibited superior anti-tumour therapeutic efficiency.

Perfluorooctyl bromide nanoemulsions holding MnO2 nanoparticles with dual-modality imaging and glutathione depletion enhanced HIFU-eliciting tumor immunogenic cell death

Tumor-targeted immunotherapy is a remarkable breakthrough, offering the inimitable advantage of specific tumoricidal effects with reduced immune-associated cytotoxicity. However, existing platforms suffer from low efficacy, inability to induce strong immunogenic cell death (ICD), and restrained capacity of transforming immune-deserted tumors into immune-cultivated ones. Here, an innovative platform, perfluorooctyl bromide (PFOB) nanoemulsions holding MnO2 nanoparticles (MBP), was developed to orchestrate cancer immunotherapy, serving as a theranostic nanoagent for MRI/CT dual-modality imaging and advanced ICD. By simultaneously depleting the GSH and eliciting the ICD effect via high-intensity focused ultrasound (HIFU) therapy, the MBP nanomedicine can regulate the tumor immune microenvironment by inducing maturation of dendritic cells (DCs) and facilitating the activation of CD8+ and CD4+ T cells. The synergistic GSH depletion and HIFU ablation also amplify the inhibition of tumor growth and lung metastasis. Together, these findings inaugurate a new strategy of tumor-targeted immunotherapy, realizing a novel therapeutics paradigm with great clinical significance.

Discrimination of dopamine by an electrode modified with negatively charged manganese dioxide nanoparticles decorated on a poly(3,4 ethylenedioxythiophene)/reduced graphene oxide composite.

A unique nanocomposite was fabricated using negatively charged manganese dioxide nanoparticles, poly (3,4-ethylenedioxythiophene) and reduced graphene oxide (MnO2/PEDOT/rGO). The nanocomposite was deposited on a glassy carbon electrode (GCE) functionalized with amino groups. The modified GCE was used to electrochemically detect dopamine (DA). The surface morphology, charge effect and electrochemical behaviours of the modified GCE were characterized by scanning electron microscopy, energy dispersive X-ray analysis (EDX), cyclic voltammetry and electrochemical impedance spectroscopy, respectively. The MnO2/PEDOT/rGO/GCE exhibited excellent performance towards DA sensing with a linear range between 0.05 and 135 µM with a lowest detection limit of 30 nM (S/N = 3). Selectivity towards DA was high in the presence of high concentrations of the typical interferences ascorbic acid and uric acid. The stability and reproducibility of the electrode were good. The sensor accurately determined DA in human serum. The synergic effect of the multiple components of the fabricated nanocomposite were critical to the good DA sensing performance. rGO provided a conductive backbone, PEDOT directed the uniform growth of MnO2 and adsorbed DA via pi-pi and electrostatic interaction, while the negatively charged MnO2 provided adsorption and catalytic sites for protonated DA. This work produced a promising biosensor that sensitively and selectively detected DA.

Photoacoustic and Magnetic Resonance Imaging of Hybrid Manganese Dioxide-Coated Ultra-small NaGdF4 Nanoparticles for Spatiotemporal Modulation of Hypoxia in Head and Neck Cancer.

There is widespread interest in developing agents to modify tumor hypoxia in head and neck squamous cell carcinomas (HNSCC). Here, we report on the synthesis, characterization, and potential utility of ultra-small NaYF4:Nd3+/NaGdF4 nanocrystals coated with manganese dioxide (usNP-MnO2) for spatiotemporal modulation of hypoxia in HNSCC. Using a dual modality imaging approach, we first visualized the release of Mn2+ using T1-weighted magnetic resonance imaging (MRI) and modulation of oxygen saturation (%sO2) using photoacoustic imaging (PAI) in vascular channel phantoms. Combined MRI and PAI performed in patient-derived HNSCC xenografts following local and systemic delivery of the hybrid nanoparticles enabled mapping of intratumoral nanoparticle accumulation (based on T1 contrast enhancement) and improvement in tumor oxygenation (increased %sO2) within the tumor microenvironment. Our results demonstrate the potential of hybrid nanoparticles for the modulation of tumor hypoxia in head and neck cancer. Our findings also highlight the potential of combined MRI-PAI for simultaneous mapping nanoparticle delivery and oxygenation changes in tumors. Such imaging methods could be valuable in the precise selection of patients that are likely to benefit from hypoxia-modifying nanotherapies.

ORR in Non-Aqueous Solvent for Li-Air Batteries: The Influence of Doped MnO2-Nanoelectrocatalyst.

One of the major drawbacks in Lithium-air batteries is the sluggish kinetics of the oxygen reduction reaction (ORR). In this context, better performances can be achieved by adopting a suitable electrocatalyst, such as MnO2. Herein, we tried to design nano-MnO2 tuning the final ORR electroactivity by tailoring the doping agent (Co or Fe) and its content (2% or 5% molar ratios). Staircase-linear sweep voltammetries (S-LSV) were performed to investigate the nanopowders electrocatalytic behavior in organic solvent (propylene carbonate, PC and 0.15 M LiNO3 as electrolyte). Two percent Co-doped MnO2 revealed to be the best-performing sample in terms of ORR onset shift (of ~130 mV with respect to bare glassy carbon electrode), due to its great lattice defectivity and presence of the highly electroactive γ polymorph (by X-ray diffraction analyses, XRPD and infrared spectroscopy, FTIR). 5% Co together with 2% Fe could also be promising, since they exhibited fewer diffusive limitations, mainly due to their peculiar pore distribution (by Brunauer-Emmett-Teller, BET) that disfavored the cathode clogging. Particularly, a too-high Fe content led to iron segregation (by energy dispersive X-ray spectroscopy, EDX, X-ray photoelectron spectroscopy, XPS and FTIR) provoking a decrease of the electroactive sites, with negative consequences for the ORR.

Multifunctional PVCL nanogels with redox-responsiveness enable enhanced MR imaging and ultrasound-promoted tumor chemotherapy.

Development of versatile nanoplatforms that simultaneously integrate therapeutic and diagnostic features for stimuli-responsive delivery to tumors remains a great challenge. In this work, we report a novel intelligent redox-responsive hybrid nanosystem composed of MnO2 nanoparticles (NPs) and doxorubicin (DOX) co-loaded within poly(N-vinylcaprolactam) nanogels (PVCL NGs) for magnetic resonance (MR) imaging-guided and ultrasound-targeted microbubble destruction (UTMD)-promoted tumor chemotherapy. Methods: PVCL NGs were first synthesized via a precipitation polymerization method, decorated with amines using ethylenediamine, and loaded with MnO2 NPs through oxidation with permanganate and DOX via physical encapsulation and Mn-N coordination bonding. The as-prepared DOX/MnO2@PVCL NGs were well characterized. UTMD-promoted cellular uptake and therapeutic efficacy of the hybrid NGs were assessed in vitro, and a xenografted tumor model was used to test the NGs for MR imaging and UTMD-promoted tumor therapy in vivo.Results: The as-prepared DOX/MnO2@PVCL NGs with a size of 106.8 nm display excellent colloidal stability, favorable biocompatibility, and redox-responsiveness to the reductive intracellular environment and tumor tissues having a relatively high glutathione (GSH) concentration that can trigger the synchronous release of Mn2+ for enhanced T1-weighted MR imaging and DOX for enhanced cancer chemotherapy. Moreover, the DOX/MnO2@PVCL NGs upon the UTMD-promotion exhibit a significantly enhanced tumor growth inhibition effect toward subcutaneous B16 melanoma owing to the UTMD-improved cellular internalization and tumor penetration. Conclusion: Our work thereby proposes a promising theranostic nanoplatform for stimuli-responsive T1-weighted MR imaging-guided tumor chemotherapy.

Sonication enhances the stability of MnO2 nanoparticles on silk film template for enzyme mimic application.

We have developed an in-situ method using sonication (3 mm probe sonicator, 30 W, 20 kHz) and auto-reduction (control) to study the mechanism of the formation of manganese dioxide (MnO2) on a solid template (silk film), and its resulting enzymatic activity on tetramethylbenzidine (TMB) substrate. The fabrication of the silk film was first optimized for stability (no degradation) and optical transparency. A factorial approach was used to assess the effect of sonication time and the initial concentration of potassium permanganate (KMnO4). The result indicated a significant correlation with a fraction of KMnO4 consumed and MnO2 formation. Further, we found that the optimal process conditions to obtain a stable silk film with highly catalytic MnO2 nanoparticles (NPs) was 30 min of sonication in the presence of 0.5 mM of KMnO4 at a temperature of 20-24 °C. Under the optimal condition, we monitored in-situ the formation of MnO2 on the silk film, and after thorough rinsing, the in-situ catalysis of 0.8 mM of TMB substrate. For control, we used the auto-reduction of KMnO4 onto the silk film after about 16 h. The result from single-wavelength analysis confirmed the different kinetics rates for the formation of MnO2 via sonication and auto-reduction. The result from the multivariate component analysis indicated a three components route for sonication and auto-reduction to form MnO2-Silk. Overall, we found that the smaller size, more mono-dispersed, and deeper buried MnO2 NPs in silk film prepared by sonication, conferred a higher catalytic activity and stability to the hybrid material.

Free-standing cellulose film containing manganese dioxide nanoparticles and its use in discoloration of indigo carmine dye.

In this study, we report the production of a free-standing film of non-modified cellulose impregnated with 12 wt.% of MnO2 nanoparticles with less than 100 nm in size. The method here described can be applied to the immobilization of different types of nanoparticles. The film was prepared by dissolving microcrystalline cellulose in an ionic liquid followed by its regeneration by adding water to the former solution. Then, the wet film was impregnated with the nanoparticles by dipping it in a MnO2 dispersion. Electron microscopy images revealed manganese dioxide nanoparticles distributed not only at the film surface but also in its interior. The cellulose film impregnated with MnO2 nanoparticles was capable of efficiently discolouring an Indigo Carmine dye solution in 25 min upon ambient light. The film was easily removed from the dye solution and repeatedly reused for at least 10 times without losing its discolouring efficiency.

Cascade catalytic nanoplatform for enhanced starvation and sonodynamic therapy.

Background: Sonodynamic therapy (SDT) has emerged as an alternative to the traditional treatments of cancer. However, the oxygen consumption induced by SDT and glucose oxidase (GOx) mediated starvation therapy would worsen the hypoxic tumor environment, which further impeded therapeutic efficacy. Purpose: To develop a nanoplatform and investigate its anti-cancer mechanism for enhanced starvation and SDT.Methods: We constructed a cascade catalytic nanoplatform based on GOx modified the mesoporous MnO2 NPs loaded with hematoporphyrin monomethyl ether (HMME), which were designated as GOx-MnO2/HMME. We characterized them for their catalytic activity, and investigate the magnetic resonance imaging and anti-tumor efficiency in vitro and in vivo.Results: MnO2 NPs with catalase-like activity could oxidize H2O2 under acid condition to produce O2, which not only in turn was supplied to the glucose-depletion reaction for an efficient starvation therapy, but also enhanced the 1O2 generation for HMME mediated SDT effect. In addition, the released Mn2+ ions in the system were able to enhance the MRI signal. Both in vitro and in vivo experiments suggested the cascade catalytic-therapeutic effect between GOx, MnO2 NPs and HMME, demonstrating the enhanced starvation and SDT.

Biosynthesis and characterization of magnesium oxide and manganese dioxide nanoparticles using Matricaria chamomilla L. extract and its inhibitory effect on Acidovorax oryzae strain RS-2.

Bacterial brown stripe (BBS) is one of the most economically important diseases of rice caused by Acidovorax oryzae (Ao). In order to ensure food security and safe consumption, the use of non-chemical approach is necessary. In this study, MgO and MnO2 were synthesized using chamomile flower extract. The synthesized MgO and MnO2 nanoparticles were characterized by UV-Visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, transmission/scanning electron microscopy. The sizes were 18.2 and 16.5 nm for MgO and MnO2 nanoparticles, respectively. The MgO and MnO2 nanoparticles reduced the growth of Ao strain RS-2 by 62.9 and 71.3%, respectively. Also, the biofilm formation and swimming motility were significantly reduced compared to the control. The antibacterial mechanisms of MgO and MnO2 nanoparticles against RS-2 reveals that MgO and MnO2 nanoparticles penetrated the cells and destroyed the cell membrane leading to leakage of cytoplasmic content. Also, the flow cytometry observation reveals that the apoptotic cell ratio of RS-2 increased from 0.97% to 99.52 and 99.94% when treated with MgO and MnO2 nanoparticles, respectively. Altogether, the results suggest that the synthesized MgO and MnO2 nanoparticles could serve as an alternative approach method for the management of BBS.

Manganese dioxide nanoparticles/activated carbon composite as efficient UV and visible-light photocatalyst.

Manganese dioxide nanoparticles/activated carbon (MnO2/AC) composites and manganese dioxide nanoparticles (MnO2 NPs) are prepared through chemical reduction method. Morphological study shows that MnO2 NPs had cylindrical and spherical shape. The morphological study also revealed that MnO2 NPs were well dispersed on AC while neat Mn NPs present both in dispersed and in agglomerated form. The FT-IR study confirms the synthesis of MnO2 NPs. Zetasizer study presented that the Mn NPs had uniform size and below 100 nm in size and had zeta potential of - 20 mV, which represent its stability in the suspension form. The synthesized Mn/AC composite and Mn NPs were utilized as photocatalysts for the photodegradation of Congo red (CR) dye. The degradation study shows that MnO2/AC composite degraded CR dye more efficiently than MnO2 NPs under UV and normal light irradiation. The efficient degradation of dye by Mn/AC composite is due to the synergistic effect between dye adsorption on AC and rapid photodegradation by supported MnO2 NPs. The results revealed that Mn/AC composite degraded about 98.53% of CR dye within 5 min while MnO2 NPs degraded 66.57% of dye within the same irradiation time. The recycled catalyst also significantly degraded dye which verifies its sustainability. The effect of catalyst dosage and initial dye concentration was conducted. The degradation rate of dye was found drastically faster in tap water (in presence of catalyst), which might be due to the presence of various mineral ions in the tap water.

Oxygen-generating Hybrid Polymeric Nanoparticles with Encapsulated Doxorubicin and Chlorin e6 for Trimodal Imaging-Guided Combined Chemo-Photodynamic Therapy.

The combination of chemotherapy with photodynamic therapy (PDT) has attracted broad attention as it can overcome limitations of conventional chemo-treatment by using different modes of action. However, the efficacy of PDT to treat solid tumors is severely affected by hypoxia in tumors. Methods: In this study, we developed oxygen-generating theranostic nanoparticles (CDM NPs) by hierarchically assembling doxorubicin (DOX), chlorin e6 (Ce6) and colloidal manganese dioxide (MnO2) with poly (ε-caprolactone-co-lactide)-b-poly (ethylene glycol)-b-poly (ε-caprolactone-co-lactide) for treating breast cancer. The in vitro and in vivo antitumor efficacy and imaging performance were investigated. Results: The theranostic nanoparticles showed high stability and biocompatibility both in vitro and in vivo. MnO2 within the nanoparticles could trigger decomposition of excessive endogenous H2O2 in the tumor microenvironment to generate oxygen in-situ to relieve tumor hypoxia. With enhanced oxygen generation, the PDT effect was significantly improved under laser-irradiation. More importantly, this effect together with that of DOX was able to dramatically promote the combined chemotherapy-PDT efficacy of CDM NPs in an MCF-7 tumor-bearing mouse model. Furthermore, the real-time tumor accumulation of the nanocomposites could be monitored by fluorescence imaging, photoacoustic (PA) imaging and magnetic resonance imaging (MRI). Conclusion: The designed CDM NPs are expected to provide an alternative way of improving antitumor efficacy by combined chemo-PDT further enhanced by oxygen generation, and would have broad applications in cancer theranostics.

Redox-Responsive Manganese Dioxide Nanoparticles for Enhanced MR Imaging and Radiotherapy of Lung Cancer.

In this study, we synthesized manganese dioxide nanoparticles (MnO2 NPs) stabilized with biocompatible polymers (polyvinylpyrrolidone and polyacrylic acid) and analyzed their effect on non-small cell lung cancer (NSCLC) cells with or without gefitinib resistance in vitro. MnO2 NPs showed glutathione (GSH)-responsive dissolution and subsequent enhancement in magnetic resonance (MR) imaging. Of note, treatment with MnO2 NPs induced significant cytotoxic effects on NSCLC cells, and additional dose-dependent therapeutic effects were obtained upon X-ray irradiation. Normal cells treated with MnO2 NPs were viable at the tested concentrations. In addition, increased therapeutic efficacy could be achieved when the cells were treated with MnO2 NPs in hypoxic conditions. Therefore, we conclude that the use of MnO2 NPs in MR imaging and combination radiotherapy may be an efficient strategy for the imaging and therapy of NSCLC.