Manganese-coordinated nanoparticle with high drug-loading capacity and synergistic photo-/immuno-therapy for cancer treatments.

Stimulator of interferon genes (STING) agonists have shown promise in cancer treatment by stimulating the innate immune response, yet their clinical potential has been limited by inefficient cytosolic entry and unsatisfactory pharmacological activities. Moreover, aggressive tumors with "cold" and immunosuppressive microenvironments may not be effectively suppressed solely through innate immunotherapy. Herein, we propose a multifaceted immunostimulating nanoparticle (Mn-MC NP), which integrates manganese II (Mn2+) coordinated photosensitizers (chlorin e6, Ce6) and STING agonists (MSA-2) within a PEGylated nanostructure. In Mn-MC NPs, Ce6 exerts potent phototherapeutic effects, facilitating tumor ablation and inducing immunogenic cell death to elicit robust adaptive antitumor immunity. MSA-2 activates the STING pathway powered by Mn2+, thereby promoting innate antitumor immunity. The Mn-MC NPs feature a high drug-loading capacity (63.42 %) and directly ablate tumor tissue while synergistically boosting both adaptive and innate immune responses. In subsutaneous tumor mouse models, the Mn-MC NPs exhibit remarkable efficacy in not only eradicating primary tumors but also impeding the progression of distal and metastatic tumors through synergistic immunotherapy. Additionally, they contribute to preventing tumor recurrence by fostering long-term immunological memory. Our multifaceted immunostimulating nanoparticle holds significant potential for overcoming limitations associated with insufficient antitumor immunity and ineffective cancer treatment.

Interfacial interaction mechanism between Mn doped highly conjugated biochar and berberine hydrochloride.

MnSO4-modified biochar (Mn-BC) was synthesized to remove berberine hydrochloride (BH) from wastewater by utilizing tea waste as raw material and MnSO4 as modifier. Brunel Emmett Taylor (BET) analysis reveals that the specific surface area (SSA) and average pore size (Dave) of Mn-BC are 1.4 and 7 times higher than those of pristine biochar apart, attributing to the dissociation effect can promote the dispersion of MnSO4 in the pores of the biochar. Meanwhile, the doping of Mn not only introduces additional oxygen-containing functional groups (OCFGs), but also modulates the π electron density. Furthermore, Response surface method (RSM) analysis reveals that Mn-BC dosage has the most significant effect on BH removal, followed by BH concentration and pH value. Kinetic and isothermal studies reveal that the BH adsorption process of Mn-BC was mainly dominated by chemical and monolayer adsorption. Meanwhile, density functional theory (DFT) calculations confirm the contribution of Mn doping to the conjugation effect in the adsorption system. Originally proposed Mn-BC is one potentially propitious material to eliminate BH from wastewater, meanwhile this also provides a newfangled conception over the sustainable utilization of tea waste resources.

Investigation into enhanced performance of toluene and Hg0 stimulative abatement over Cr-Mn oxides co-modified columnar activated coke.

In this study, a string of Cr-Mn co-modified activated coke catalysts (XCryMn1-y/AC) were prepared to investigate toluene and Hg0 removal performance. Multifarious characterizations including XRD, TEM, SEM, in situ DRIFTS, BET, XPS and H2-TPR showed that 4%Cr0.5Mn0.5/AC had excellent physicochemical properties and exhibited the best toluene and Hg0 removal efficiency at 200℃. By varying the experimental gas components and conditions, it was found that too large weight hourly space velocity would reduce the removal efficiency of toluene and Hg0. Although O2 promoted the abatement of toluene and Hg0, the inhibitory role of H2O and SO2 offset the promoting effect of O2 to some extent. Toluene significantly inhibited Hg0 removal, resulting from that toluene was present at concentrations orders of magnitude greater than mercury's or the catalyst was more prone to adsorb toluene, while Hg0 almost exerted non-existent influence on toluene elimination. The mechanistic analysis showed that the forms of toluene and Hg0 removal included both adsorption and oxidation, where the high-valent metal cations and oxygen vacancy clusters promoted the redox cycle of Cr3+ + Mn3+/Mn4+ ↔ Cr6+ + Mn2+, which facilitated the conversion and replenishment of reactive oxygen species in the oxidation process, and even the CrMn1.5O4 spinel structure could provide a larger catalytic interface, thus enhancing the adsorption/oxidation of toluene and Hg0. Therefore, its excellent physicochemical properties make it a cost-effective potential industrial catalyst with outstanding synergistic toluene and Hg0 removal performance and preeminent resistance to H2O and SO2.

Support electron inductive effect of Pd-Mn/Ni foam catalyst for robust electrocatalytic hydrodechlorination.

Structural regulation of Pd-based electrocatalytic hydrodechlorination (EHDC) catalyst for constructing high-efficient cathode materials with low noble metal content and high atom utilization is crucial but still challenging. Herein, a support electron inductive effect of Pd-Mn/Ni foam catalyst was proposed via in-situ Mn doping to optimize the electronic structure of the Ni foam (NF), which can inductive regulation of Pd for improving the EHDC performance. The mass activity and current efficiency of Pd-Mn/NF catalyst are 2.91 and 1.34 times superior to that of Pd/NF with 2,4-dichlorophenol as model compound, respectively. The Mn-doped interlayer optimized the electronic structure of Pd by bringing the d-state closer to the Fermi level than Pd on the NF surface, which optimizied the binding of EHDC intermediates. Additionally, the Mn-doped interlayer acted as a promoter for generating H* and accelerating the EHDC reaction. This work presents a simple and effective regulation strategy for constructing high-efficient cathode catalyst for the EHDC of chlorinated organic compounds.

Mn/S diatomic sites in C3N4 to enhance O2 activation for photocatalytic elimination of emerging pollutants.

Oxygen activation leading to the generation of reactive oxygen species (ROS) is essential for photocatalytic environmental remediation. The limited efficiency of O2 adsorption and reductive activation significantly limits the production of ROS when employing C3N4 for the degradation of emerging pollutants. Doping with metal single atoms may lead to unsatisfactory efficiency, due to the recombination of photogenerated electron-hole pairs. Here, Mn and S single atoms were introduced into C3N4, resulting in the excellent photocatalytic performances. Mn/S-C3N4 achieved 100% removal of bisphenol A, with a rate constant 11 times that of pristine C3N4. According to the experimental results and theoretical simulations, S-atoms restrict holes, facilitating the photo-generated carriers' separation. Single-atom Mn acts as the O2 adsorption site, enhancing the adsorption and activation of O2, resulting the generation of ROS. This study presents a novel approach for developing highly effective photocatalysts that follows a new mechanism to eliminate organic pollutants from water.

Manganese-arginine nanozymes as oxidase mimics for smartphone-based intelligent detection of 4'-O-methylpyridoxine.

By self-assembly of MnCl2 and arginine under alkaline conditions, ultra-small MnArg nanoparticles were successfully constructed as oxidase (OXD) mimics for intelligent detection of the Ginkgo toxin 4'-O-methylpyridoxal (MPN). The obtained MnArg nanozymes possessed excellent OXD-like activity and thermal stability. Based on the inhibitory effect of MPN for the catalytic activity of MnArg, this system was utilized for the colorimetric sensing of MPN with a low limit of detection (LOD) of 2.16 µg mL-1. The detection  system exhibited good selectivity against other potential interferents. FTIR data showed that the presence of MPN binds with MnArg and shields the active sites, thereby interfering with the oxidase-like activity. Combined with a smartphone and the ColorMax software, this nanozyme-based intelligent detection platform could effectively detect MPN with a LOD of 2.1 µg mL-1. Our MnArg nanozyme-based system was applied to detect real ginkgo nut samples with recoveries of 92.4-108.7%, and the relative standard deviations were less than 0.7%. This work may promote the development of novel nanozymes and expand their applications in the field of food safety detection.

Two-dimensional coordination risedronate-manganese nanobelts as adjuvant for cancer radiotherapy and immunotherapy.

The irradiated tumor itself represents an opportunity to establish endogenous in situ vaccines. However, such in situ cancer vaccination (ISCV) triggered by radiation therapy (RT) alone is very weak and hardly elicits systemic anticancer immunity. In this study, we develop two-dimensional risedronate-manganese nanobelts (RMn-NBs) as an adjuvant for RT to address this issue. RMn-NBs exhibit good T2 magnetic resonance imaging performance and enhanced Fenton-like catalytic activity, which induces immunogenic cell death. RMn-NBs can inhibit the HIF-1α/VEGF axis to empower RT and synchronously activate the cGAS/STING pathway for promoting the secretion of type I interferon, thereby boosting RT-triggered ISCV and immune checkpoint blockade therapy against primary and metastatic tumors. RMn-NBs as a nano-adjuvant for RT show good biocompatibility and therapeutic efficacy, presenting a promising prospect for cancer radiotherapy and immunotherapy.

Hyaluronic acid modified Cu/Mn-doped metal-organic framework nanocatalyst for chemodynamic therapy.

Chemodynamic therapy (CDT) is a new method for cancer treatment that produces highly toxic reactive oxygen species (ROS) in the tumor microenvironment to induce cancer cell apoptosis or necrosis. However, the therapeutic effect of CDT is often hindered by intracellular H2O2deficiency and the activity of antioxidants such as glutathione (GSH). In this study, a nano-catalyst HCM was developed using a self-assembled Cu/Mn-doped metal-organic framework, and its surface was modified with hyaluronic acid to construct a tumor-targeting CDT therapeutic agent with improved the efficiency and specificity. Three substances HHTP (2, 3, 6, 7, 10, 11-hexahydroxybenzophenanthrene), Cu2+, and Mn2+were shown to be decomposed and released under weakly acidic conditions in tumor cells. HHTP produces exogenous H2O2in the presence of oxygen to increase the H2O2content in tumors, Cu2+reduces GSH content and generates Cu+in the tumor, and Cu+and Mn2+catalyze H2O2to produce ∙OH in a Fenton-like reaction. Together, these three factors change the tumor microenvironment and improve the efficiency of ROS production. HCM showed selective and efficient cytotoxicity to cancer cells, and could effectively inhibit tumor growthin vivo, indicating a good CDT effect.

Design, Synthesis and Characterization of Mn(II)Cysteine-Tyrosine Dithiocarbamate Complex for against the Cancer on MCF-7 Breast Cancer Cell Line.

OBJECTIVE: Breast cancer is the most frequently diagnosed cancer and the second cause of death worldwide. The drug often used for chemotherapy is cisplatin. However, the drug cisplatin has a number of problems, including lack of selectivity, undesirable side effects, resistance, and toxicity in the body. So research is carried out on new drug compounds with low toxicity by designing in silico with molecular docking. METHODS: Mn(II) Cysteine-Tyrosine dithiocarbamate is a new complex molecule whose research involves several steps, such as in-silico molecular docking testing with target proteins, ADMET then synthesis, characterization and in-vitro MCF-7 cells for anticancer drugs. The synthesis process involves the reaction of manganese metal with tyrosine, cysteine, CS2 and KOH. Characterization tests have been carried out including FT-IR spectroscopy, SEM-EDS, UV Vis, conductivity, melting point and XRD. RESULT: Confirm the structure of the compound using UV Vis, obtained orbitals π to π* and n to π* in the group N = C = S is represented by the absorption at 400 nm and 600 nm, FT-IR with the results obtained by the functional groups O-H, N-H, C =N and C=S. In vitro test results showed morphological changes (apoptosis) in MCF-7 cancer cells starting from 250 µg/mL and an IC50 value of 416.90 µg/mL. Molecular docking studies of the Mn(II)Cysteine-Tyrosine dithiocarbamate complex were identified with 4,4',4''-[(2R)-butane-1,1,2-triyl]triphenol - Estrogen α which showed an active site with amino acid residues GLU323, GLU385, VAL446, ILE514, TRP360, LYS449, MET388, MET357, PHE445, VAL392 and ILE389. Hydrophobic and hydrophobic bonds are seen in Mn(II)Cysteine-Tyrosine dithiocarbamate - Estrogen α has a bond energy of -77.5372 kJ/mol. CONCLUSION: Despite having a high H-bond interaction intensity, the chemical does not have a powerful enough anticancer impact. Despite the produced compound's low bioactivity, this study should offer important new understandings into how molecular structure affects anticancer activity.

Development of a New Permanganate/Chlorite Process for Water Decontamination.

Development of new technologies with strong selectivity for target pollutants and low sensitivity toward a water matrix remains challenging. Herein, we introduced a novel strategy that used chlorite as an activator for Mn(VII) at pH 4.8, turning the inert reactivity of the pollutants toward Mn(VII) into a strong reactivity. This paved a new way for triggering reactions in water decontamination. By utilizing sulfamethoxazole (SMX) as a typical pollutant, we proposed coupled pathways involving electron transfer across hydrogen bonds (TEHB) and oxidation by reactive manganese species. The results indicated that a hydrogen bonding complex, SMX-ClO2-*, formed through chlorite binding the amino group of SMX initially in the TEHB route; such a complex exhibited a stronger reduction capability toward Mn(VII). Chlorite, in the hydrogen bonding complex SMX-ClO2-*, can then complex with Mn(VII). Consequently, a new reactive center (SMX-ClO2--Mn(VII)*) was formed, initiating the transfer of electrons across hydrogen bonds and the preliminary degradation of SMX. This is followed by the involvement of the generated Mn(V)-ClO2-/Mn(III) in the reduction process of Mn(VII). Such a process showed pH-dependent degradation, with a removal ratio ranging from 80% to near-stagnation as pH increased from 4.8 to 7. Combining with pKa analysis showed that the predominant forms of contaminants were crucial for the removal efficiency of pollutants by the Mn(VII)/chlorite process. The impact of the water matrix was demonstrated to have few adverse or even beneficial effects. With satisfactory performance against numerous contaminants, this study introduced a novel Mn(VII) synergistic strategy, and a new reactivity pattern focused on reducing the reduction potential of the contaminant, as opposed to increasing the oxidation potential of oxidants.

Denitrification performance of the nitrate-dependent manganese redox strain Dechloromonas sp. YZ8 under copper ion (Cu(â ¡)) stress: Promotion mechanism and immobilization efficacy.

A novel nitrate-dependent manganese (Mn) redox strain was isolated and identified as Dechloromonas sp.YZ8 in this study. The growth conditions of strain YZ8 were optimized by kinetic experiments. The nitrate (NO3--N) removal efficiency was 100.0 % at 16 h at C/N of 2.0, pH of 7.0, and Mn(II) or Mn(IV) addition of 10.0 or 500.0 mg L-1, along with an excellent Mn redox capacity. Transmission electron microscopy supported the Mn redox process inside and outside the cells of strain YZ8. When strain YZ8 was exposed to different concentrations of copper ion (Cu(II)), it turned out that moderate amounts of Cu(II) increased microbial activity and metabolic activities. Moreover, it was discovered that the appropriate amount of Cu(II) promoted the conversion of Mn(IV) and Mn(II) to Mn(III) and improved electron transfer capacity in the Mn redox system, especially the Mn redox process dominated by Mn(IV) reduction. Then, δ-MnO2 and bio-manganese oxides (BMO) produced during the reaction process have strong adsorption of Cu(II). The surface valence changes of δ-MnO2 before and after the reaction and the production of BMO, Mn(III)-rich intermediate black manganese ore (Mn3O4), and Mn secondary minerals together confirmed the Mn redox pathway. The study provided new insights into the promotion mechanism and immobilization effects of redox-coupled denitrification of Mn in groundwater under Cu(II) stress.

New insights on the Jacobsite mineral from Bahia and related synthetic manganese-ferrite nanoparticles.

Jacobsite is a relatively rare mineral of composition MnFe2O4, found in Urandi (Bahia State) in Brazil. It is also a common species in the deep-sea manganese nodules, attracting the interest of many mineral-extracting companies. Because of its spinel constitution similar to magnetite, Jacobsite is commonly called a manganese-ferrite. However, the manganese/iron content may vary substantially according to its origin, demanding specific studies in each case. The Jacobsite mineral inspired our laboratory synthesis of the analogous manganese ferrite nanoparticles. The direct synthesis by the coprecipitation method has not been successful; however, it can be carried in the presence of citrate ions, yielding strongly magnetic nanoparticles, with a maximum magnetization of 45.6 emu.g1. Although they were structurally identical to Jacobsite, the mineral from Bahia exhibited a rather weak magnetism, because it involves a ferrimagnetic coupling. For this reason, the synthetic method seems to provide a better way of obtaining strongly magnetic manganese ferrites. These magnetic nanoparticles have been investigated in detail, including their interaction with diatoms, providing interesting magnetic bio-silicate carriers in drug delivery.

Metal-organic cage as a theranostic nanoplatform for magnetic resonance imaging guided chemodynamic therapy.

Rationale: Theranostic nanoplatforms exert a vital role in facilitating concurrent real-time diagnosis and on-demand treatment of diseases, thereby making contributions to the improvement of therapeutic efficacy. Nevertheless, the structural intricacy and the absence of well-defined integration of dual functionality persist as challenges in the development of theranostic nanoplatforms. Methods: We develop an atomically precise theranostic nanoplatform based on metal-organic cage (MOC) to provide magnetic resonance imaging (MRI) guided chemodynamic therapy (CDT) for cancer therapy and assess the theranostic performance both in vitro and in vivo. Through UV-vis spectroscopy, electron paramagnetic resonance (EPR), confocal microscopy, flow cytometry, immunofluorescence staining, and western blotting, the ability of MOC-Mn to generate •OH and the subsequent inhibition of HeLa cells was confirmed. Results: The MOC-Mn composed of manganese and calixarene was successfully synthesized and comprehensively characterized. The catalytic activity of manganese within MOC-Mn facilitated the efficient generation of hydroxyl radicals (•OH) through a Fenton-like reaction, leveraging the high concentrations of hydrogen peroxide in the tumor microenvironment (TME). Additionally, its capacity to prolong the T1 relaxation time and augment the MR signal was observed. The theranostic efficacy was verified via rigorous in vitro and in vivo experiments, indicating that MOC-Mn offered clearer visualization of tumor particulars and substantial suppression of tumor growth. Conclusion: This study showcases a precise MRI-guided CDT theranostic nanoplatform for cancer therapy, thereby promoting the advancement of precise nanomedicine and structure-function research.

Rapid detection of tertiary butylated hydroquinone in food samples using Mn-MOF@f-CNF composite-modified screen-printed electrode.

Hydroquinone-based organic molecules are often used as unavoidable preservatives in the food industry. Among these additives, tertiary butylated hydroquinone (TBHQ) is widely employed as a preservative in various processed foods. However, the potential health risks associated with the excessive presence of TBHQ in food products have raised significant concerns. To address this pressing issuea novel binder-free composite composed of a manganese metal-organic framework and functionalized carbon nanofibers (Mn-MOF/f-CNF) has been developed as an electrode modifier for the ultrasensitive detection of TBHQ in food samples. The Mn-MOF/f-CNF composite was achieved using the ultrasonication method, revealing a lamellar sheet-like structure of the Mn-MOF and the curly thread-like fibrous structure of f-CNF. The developed Mn-MOF/f-CNF/SPE sensor system resulted in well-defined redox signals for TBHQ detection in a neutral pH solution. Compared to the unmodified SPE system, the modified system showed approximately a 300 mV reduction in overpotential and a twofold increase in peak current signal for TBHQ detection. The Mn-MOF/f-CNF/SPE sensor system showed a linear concentration window of 0.01 to 800 µM with a sensitivity of 6.28 µA µM-1 cm-2 and the obtained detection limit was 1.36 nM. Additionally, the proposed sensor displayed excellent reproducibility and repeatable results with an RSD of less than 5%. The real-time applicability of the Mn-MOF/f-CNF/SPE sensor system was demonstrated using real samples such as potato chips and instant noodles, showing excellent results with a recovery range of 95.1-98.5%.

Substitution of the mononuclear, non-heme iron cofactor in lipoxygenases for structural studies.

This Chapter describes methods for the biosynthetic substitution of the mononuclear, non-heme iron in plant and animal lipoxygenases (LOXs). Substitution of this iron center for a manganese ion results in an inactive, yet faithful structural surrogate of the LOX enzymes. This metal ion substitution permits structural and dynamical studies of enzyme-substrate complexes in solution and immobilized on lipid membrane surfaces. Representative procedures for two LOXs, soybean lipoxygenase (SLO) from plants and human epithelial 15-lipoxygenase-2 (15-LOX-2) from mammals, are described as examples.

Bidentate Substrate Binding Mode in Oxalate Decarboxylase.

Oxalate decarboxylase is an Mn- and O2-dependent enzyme in the bicupin superfamily that catalyzes the redox-neutral disproportionation of the oxalate monoanion to form carbon dioxide and formate. Its best-studied isozyme is from Bacillus subtilis where it is stress-induced under low pH conditions. Current mechanistic schemes assume a monodentate binding mode of the substrate to the N-terminal active site Mn ion to make space for a presumed O2 molecule, despite the fact that oxalate generally prefers to bind bidentate to Mn. We report on X-band 13C-electron nuclear double resonance (ENDOR) experiments on 13C-labeled oxalate bound to the active-site Mn(II) in wild-type oxalate decarboxylase at high pH, the catalytically impaired W96F mutant enzyme at low pH, and Mn(II) in aqueous solution. The ENDOR spectra of these samples are practically identical, which shows that the substrate binds bidentate (κO, κO') to the active site Mn(II) ion. Domain-based local pair natural orbital coupled cluster singles and doubles (DLPNO-CCSD) calculations of the expected 13C hyperfine coupling constants for bidentate bound oxalate predict ENDOR spectra in good agreement with the experiment, supporting bidentate bound substrate. Geometry optimization of a substrate-bound minimal active site model by density functional theory shows two possible substrate coordination geometries, bidentate and monodentate. The bidentate structure is energetically preferred by ~4.7 kcal/mol. Our results revise a long-standing hypothesis regarding substrate binding in the enzyme and suggest that dioxygen does not bind to the active site Mn ion after substrate binds. The results are in agreement with our recent mechanistic hypothesis of substrate activation via a long-range electron transfer process involving the C-terminal Mn ion.

Plant extract mediated in-situ synthesis of iron/manganese alginate hydrosphere and its excellent recovery of rare earth elements in mine wastewater.

The recovery of rare earth elements (REEs) is a major issue based on environmental governance and sustainable resource utilization. In this study, we developed a novel hydrogel material (Fe/Mn@ALG) by anchoring Fe/Mn NPs on alginate spheres, where Fe/Mn NPs were in-situ synthesized using Euphorbia cochinchensi leaf extract as reduced and protection agents. The Fe/Mn@ALG was applied directly to real mine wastewater, generating efficient and selective recovery of REEs with the coexistence of numerous competing metal ions. As results have shown, Fe/Mn@ALG was a useful adsorbent for REEs with an adsorption efficiency 78.62 % achieved, which was also confirmed by distribution coefficients (Kd), up to 2451.66 mL·g-1. Furthermore, Fe/Mn@ALG exhibited preferential response to REEs over other metal ions with the separation factor (SF) being up to 240. This great adsorption performance and selectivity toward REEs were attributed to its specific surface area, oxygen-rich functional groups and negatively charged surface in acid wastewater. Furthermore, REEs could be greatly desorbed from Fe/Mn@ALG with output concentration being three times higher than the initial concentration. Additionally, Fe/Mn@ALG maintained its good adsorption performance with efficiency reaching 72.24 % after five reuses. Overall, Fe/Mn@ALG can be considered as a promising candidate for wastewater remediation and sustainable management of resources.

Rational Design of an Artificial Metalloenzyme by Constructing a Metal-Binding Site Close to the Heme Cofactor in Myoglobin.

In this study, we constructed a metal-binding site close to the heme cofactor in myoglobin (Mb) by covalently attaching a nonnative metal-binding ligand of bipyridine to Cys46 through the F46C mutation in the heme distal site. The X-ray structure of the designed enzyme, termed F46C-mBpy Mb, was solved in the Cu(II)-bound form, which revealed the formation of a heterodinuclear center of Cu-His-H2O-heme. Cu(II)-F46C-mBpy Mb exhibits not only nitrite reductase reactivity but also cascade reaction activity involving both hydrolysis and oxidation. Furthermore, F46C-mBpy Mb displays Mn-peroxidase activity by the oxidation of Mn2+ to Mn3+ using H2O2 as an oxidant. This study shows that the construction of a nonnative metal-binding site close to the heme cofactor is a convenient approach to creating an artificial metalloenzyme with a heterodinuclear center that confers multiple functions.

Regulating Manganese-Site Electronic Structure via Reconstituting Nitrogen Coordination for Efficient Non-Oxygen-Dependent Sonocatalytic Therapy against Orthotopic Breast Cancer.

Sonocatalytic therapy (SCT) has emerged as a promising noninvasive modality for tumor treatment but is hindered by the insufficient generation of ultrasound-induced reactive oxygen species (ROS) and the hypoxic tumor microenvironments. Herein, we fabricated a carbon nanoframe-confined N-coordinated manganese single-atom sonocatalyst with a five-coordinated structure (MnN5 SA/CNF) using a phthalocyanine-mediated pyrolysis strategy. The precise coordination structure was identified by synchrotron X-ray absorption fine structure analyses. The MnN5 SA/CNF exhibits superior and nonoxygen-dependent sonocatalytic activity owing to the optimized coordination structure and cavitation effect enhanced by defects. Additionally, density functional theory studies reveal that the five-coordination structure downshifts the d-band center of Mn from -0.547 to -0.829 eV and enhances the desorption capacity for oxygen-containing intermediates, thus accelerating the catalytic process. Finally, the as-synthesized MnN5 SA/CNF demonstrates a significantly enhanced antitumor effect through mitochondrial apoptosis in an orthotopic breast cancer mouse model. This work explores the potential of SAzymes-supported biomedical interventions by leveraging enzymatic activity with sonocatalytic properties.

A manganese-doped layered double hydroxide loaded with lactate oxidase and DNA repair inhibitors for synergistically enhanced tumor immunotherapy.

Tumor immunotherapy has gained more and more attention in tumor treatment. However, the accumulation of lactic acid in tumor tissue inhibits the response of immune cells to form an immunosuppressive microenvironment (ISME). To reverse the ISME, an acid-responsive nanoplatform (termed as MLLN@HA) is reported for synergistically enhanced tumor immunotherapy. MLLN@HA is constructed by the co-loading of lactate oxidase (LOX) and DNA repair inhibitor (NU7441) in a manganese-doped layered double hydroxide (Mn-LDH), and then modified with hyaluronic acid (HA) for tumor-targeted delivery. After endocytosis by tumor cells, MLLN@HA decomposes and releases LOX, NU7441 and Mn2+ ions in the acidic tumor microenvironment. The released LOX catalyzes the conversion of lactic acid into hydrogen peroxide (H2O2), which not only alleviates the ISME, but also provides reactants for the Mn2+-mediated Fenton-like reaction to enhance chemodynamic therapy (CDT). Released NU7441 prevents CDT-induced DNA damage from being repaired, thereby increasing double-stranded DNA (dsDNA) fragments within tumor cells. Importantly, the released Mn2+ ions enhance the sensitivity of cyclic GMP-AMP synthase (cGAS) to dsDNA fragments, and activate the stimulator of interferon genes (STING) to induce an anti-tumor immune response. Such an orchestrated immune-boosting strategy ultimately achieves effective tumor growth inhibition and prevents tumor lung metastasis. STATEMENT OF SIGNIFICANCE: To improve the efficacy of tumor immunotherapy, an innovative acid-responsive MLLN@HA nanoplatform was developed for synergistically enhanced tumor immunotherapy. The MLLN@HA actively targets to tumor cells through the interaction of HA with CD44, and then degrades to release LOX, NU7441 and Mn2+ ions in the acidic tumor microenvironment. The released LOX generates H2O2 for the Mn2+-mediated Fenton reaction and reverses the ISME by consuming lactate. NU7441 prevents DNA damage repair, leading to an increased concentration of free DNA fragments, while Mn2+ ions activate the cGAS-STING pathway, enhancing the systemic anti-tumor immune response. The orchestrated immune-boosting nanoplatform effectively inhibits tumor growth and lung metastasis, presenting a promising strategy for cancer treatment.