Manganese-based nanomaterials promote synergistic photo-immunotherapy: green synthesis, underlying mechanisms, and multiple applications.

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.

Amorphous mixed-valent Mn-containing nanozyme with cocklebur-like morphology for specific colorimetric detection of cancer cells via Velcro effects.

Designing nanozymes with excellent catalytic activity through valence state engineering and defect engineering is a widely applicable strategy. However, their development is hindered by the complexity of the design strategies. In this work, we employed a simple calcination method to regulate the valence of manganese and crystalline states in manganese oxide nanozymes. The oxidase-like activity of the nanozymes was found to benefit from a mixed valence state dominated by Mn (III). And the amorphous structure with more active defect sites significantly enhanced the catalytic efficiency. Moreover, we demonstrated that amorphous mixed-valent Mn-containing (amvMn) nanozymes with unique cocklebur-like biomimetic morphology achieved specific binding to cancer cells through the Velcro effects. Subsequently, the nanozymes mediated TMB coloration through their oxidase-like activity, enabling the colorimetric detection of cancer cells. This work not only provides guidance for optimizing nanozyme performance, but also inspire the development of equipment-free visual detection methods for cancer cells.

Study on mutual harmless treatment of electrolytic manganese residue and red mud.

Electrolytic manganese residue (EMR) and red mud (RM) are solid waste by-products of the metal manganese and alumina industries, respectively. Under long-term open storage, ammonia nitrogen and soluble manganese ions in EMR and alkaline substances in RM severely pollute and harm the environment. In order to alleviate the pollution problem of EMR and RM. In this study, the alkaline substances in RM were used to treat ammonia nitrogen and soluble manganese ions in EMR. The results confirm the following suitable treatment conditions for the mutual treatment of EMR and RM: EMR-RM mass ratio = 1:1, liquid-solid ratio = 1.4:1, and stirring time = 320 min. Under these conditions, the elimination ratios of ammonia nitrogen (emitted in the form of ammonia gas) and soluble manganese ions (solidified in the form of Mn3.88O7(OH) and KMn8O16) are 85.87 and 86.63%, respectively. Moreover, the alkaline substances in RM are converted into neutral salts (Na2SO4 and Mg3O(CO3)2), achieving de-alkalinisation. The treatment method can also solidify the heavy metal ions-Cr3+, Cu2+, Ni2+, and Zn2+-present in the waste residue with leaching concentrations of 1.45 mg/L, 0.099 mg/L, 0.294 mg/L, and 0.449 mg/L, respectively. This satisfies the requirements of the Chinese standard GB5085.3-2007. In the mutual treatment of EMR and RM, the kinetics of ammonia nitrogen removal and manganese-ion solidification reactions are controlled via a combination of membrane diffusion and chemical reaction mechanisms.

Meta-omics profiling of full-scale groundwater rapid sand filters explains stratification of iron, ammonium and manganese removals.

Rapid sand filters (RSF) are an established and widely applied technology for groundwater treatment. Yet, the underlying interwoven biological and physical-chemical reactions controlling the sequential removal of iron, ammonia and manganese remain poorly understood. To resolve the contribution and interactions between the individual reactions, we studied two full-scale drinking water treatment plant configurations, namely (i) one dual-media (anthracite and quartz sand) filter and (ii) two single-media (quartz sand) filters in series. In situ and ex situ activity tests were combined with mineral coating characterization and metagenome-guided metaproteomics along the depth of each filter. Both plants exhibited comparable performances and process compartmentalization, with most of ammonium and manganese removal occurring only after complete iron depletion. The homogeneity of the media coating and genome-based microbial composition within each compartment highlighted the effect of backwashing, namely the complete vertical mixing of the filter media. In stark contrast to this homogeneity, the removal of the contaminants was strongly stratified within each compartment, and decreased along the filter height. This apparent and longstanding conflict was resolved by quantifying the expressed proteome at different filter heights, revealing a consistent stratification of proteins catalysing ammonia oxidation and protein-based relative abundances of nitrifying genera (up to 2 orders of magnitude difference between top and bottom samples). This implies that microorganisms adapt their protein pool to the available nutrient load at a faster rate than the backwash mixing frequency. Ultimately, these results show the unique and complementary potential of metaproteomics to understand metabolic adaptations and interactions in highly dynamic ecosystems.

Resin-based iron-manganese binary oxide for phosphate selective removal.

Adsorption technology can effectively remove phosphorus from water and realize phosphorus recovery. Hence, it is used to curb the eutrophication of water and alleviate the crisis caused by the shortage of phosphorus resources. Resin has been attracting increasing interest as an ideal adsorption material; however, its practical application is greatly affected by environmental factors. To solve the competitive adsorption and pore blockage caused by humic acid and coexisting ions during the removal of phosphorus by ion-exchange resin, this study has developed an iron-manganese oxide-modified resin composite adsorbent (Fe/Mn-402) based on the nanoconfinement theory. The structural characterization results of XRD, FT-IR, SEM, and XPS showed that the iron-manganese binary oxide was successfully loaded on the skeleton of the strongly alkaline anion resin and showed good stability under both neutral and alkaline conditions. The batch adsorption experiments showed that the maximum adsorption capacity of Fe/Mn-402 for phosphorus can reach up to 50.97 mg g-1 under the optimal raw material ratio (Fe:Mn = 1:1). In addition, Fe/Mn-402 shows good selectivity for phosphorus removal. Fe/Mn-402 can maintain good adsorption performance for phosphate even under high concentrations of SO42-, HCO3-, and humic acid. The regenerated Fe/Mn-402 can be recycled without any obvious change in its treatment capacity. Hence, it is suitable for stable, long-term usage. In general, this work puts forward a new idea for the development of phosphorus-removal adsorbents for the treatment of wastewater containing coexisting ions and HA.

Application of Spectroscopic Methods for the Identification of Superoxide Dismutases in Cyanobacteria.

Superoxide dismutases (SODs) belong to the group of metalloenzymes that remove superoxide anion radicals and they have been identified in three domains of life: Bacteria, Archaea and Eucarya. SODs in Synechocystis sp. PCC 6803, Gloeobacter violaceus CCALA 979, and Geitlerinema sp. ZHR1A were investigated. We hypothesized that iron (FeSOD) and/or manganese (MnSOD) dominate as active forms in these cyanobacteria. Activity staining and three different spectroscopic methods of SOD activity bands excised from the gels were used to identify a suitable metal in the separated samples. FeSODs or enzymes belonging to the Fe-MnSOD superfamily were detected. The spectroscopic analyses showed that only Fe is present in the SOD activity bands. We found FeSOD in Synechocystis sp. PCC 6803 while two forms in G. violaceus and Geitlerinema sp. ZHR1A: FeSOD1 and FeSOD2 were present. However, no active Cu/ZnSODs were identified in G. violaceus and Geitlerinema sp. ZHR1A. We have shown that selected spectroscopic techniques can be complementary to the commonly used method of staining for SOD activity in a gel. Furthermore, the occurrence of active SODs in the cyanobacteria studied is also discussed in the context of SOD evolution in oxyphotrophs.

Effect of extrusion-spheronization granulation and manganese loading on catalytic ozonation of petrochemical wastewater.

The petrochemical secondary effluent (PSE) is typical refractory wastewater derived from the petrochemical industries, which requires advanced treatment due to the strict environmental protection policies. Catalytic ozonation is one of the most widely used advanced oxidation technologies in wastewater treatment because of its high mineralization rate, in which the alumina-based catalyst usually plays an important role. Extrusion-spheronization is a promising technique for the preparation of alumina spheres because the synthesized alumina particles have high sphericity, high specific surface aera and narrow particle size distribution. In this paper, two kinds of alumina-based catalysts (catalyst A: manganese nitrate added after alumina granulation and catalyst B: manganese nitrate added into alumina powder before granulation) were prepared by the extrusion-spheronization method and used for PSE treatment by catalytic ozonation. The prepared alumina samples were characterized by Brunauer-Emmett-Teller (BET) method, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and scanning electron microscopy (SEM), while the wastewater samples were analyzed for Total organic carbon (TOC), UV254 and fluorescence spectroscopy. Results showed that manganese was uniformly distributed in both catalysts, and the specific surface area of two catalysts was 318.36 m2/g and 354.95 m2/g, respectively. Catalytic ozonation experiments were repeated nine times with each catalyst under the same conditions. The TOC removal rates for catalysts A and B in the first run were 48.88% and 49.06%, respectively, then it dropped to 28.05% for catalyst A but remained 47.81% for catalyst B after using for nine times. This implied that the long-term performance of catalyst B would be more stable than catalyst A. Similar result were found in three-dimensional fluorescence analysis. UV254 results indicated that the removal efficiency of aromatic and unsaturated substances by catalyst B was higher than catalyst A. A possible explanation is that the active component manganese oxide formed a catalyst skeleton in catalyst B, which makes it hard to dissolve. Effect of extrusion-spheronization granulation and manganese loading on advanced oxidant treatment of petrochemical wastewater.

Tumor microenvironment responsive self-cascade catalysis for synergistic chemo/chemodynamic therapy by multifunctional biomimetic nanozymes.

Chemodynamic therapy (CDT) is an emerging approach to treat cancer based on the tumor microenvironment (TME), but its limited content of endogenous hydrogen peroxide (H2O2) weakens the anticancer effects. Herein, a multifunctional biomimetic nanozyme (Se@SiO2-Mn@Au/DOX, named as SSMA/DOX) is fabricated, which undergoes TME responsive self-cascade catalysis to facilitate MRI guided enhanced chemo/chemodynamic therapy. The SSMA/DOX nanocomposites (NCs) responsively degrade in acidic conditions of tumor to release Se, DOX, Au and Mn2+. Mn2+ not only enables MRI to guided therapy, but also catalyzes the endogenous H2O2 into hydroxyl radical (˙OH) for CDT. In addition, the Au NPs continuously catalyze glucose to generate H2O2, enhancing CDT by supplementing a sufficiently reactive material and cutting off the energy supply of the tumor by consuming glucose. Simultaneously, Se enhances the chemotherapy of doxorubicin hydrochloride (DOX) and CDT by upregulating ROS in the tumor cells, achieving remarkable inhibition effect towards tumor. Moreover, SSMA/DOX NCs have good biocompatibility and degradability, which avoid long-term toxicity and side effects. Overall, the degradable SSMA/DOX NCs provide an innovative strategy for tumor microenvironment responsive self-cascade catalysis to enhance tumor therapy.

A DNA Nanocomplex Containing Cascade DNAzymes and Promoter-Like Zn-Mn-Ferrite for Combined Gene/Chemo-dynamic Therapy.

Sequential control of exogenous chemical events inside cells is a promising way to regulate cell functions and fate. Herein we report a DNA nanocomplex containing cascade DNAzymes and promoter-like Zn-Mn-Ferrite (ZMF), achieving combined gene/chemo-dynamic therapy. The promoter-like ZMF decomposed in response to intratumoral glutathione to release a sufficient quantity of metal ions, thus promoting cascade DNA/RNA cleavage and free radical generation. Two kinds of DNAzymes were designed for sequential cascade enzymatic reaction, in which metal ions functioned as cofactors. The primary DNAzyme self-cleaved the DNA chain with Zn2+ as cofactor, and produced the secondary DNAzyme; the secondary DNAzyme afterwards cleaved the EGR-1 mRNA, and thus downregulated the expression of target EGR-1 protein, achieving DNAzyme-based gene therapy. Meanwhile, the released Zn2+ , Mn2+ and Fe2+ induced Fenton/Fenton-like reactions, during which free radicals were catalytically generated and efficient chemo-dynamic therapy was achieved. In a breast cancer mouse model, the administration of DNA nanocomplex led to a significant therapeutic efficacy of tumor growth suppression.

Protein metalation in biology.

Inorganic metals supplement the chemical repertoire of organic molecules, especially proteins. This requires the correct metals to associate with proteins at metalation. Protein mismetalation typically occurs when excesses of unbound metals compete for a binding site ex vivo. However, in biology, excesses of metal-binding sites typically compete for limiting amounts of exchangeable metals. Here, we summarise mechanisms of metal homeostasis that sustain optimal metal availabilities in biology. We describe recent progress to understand metalation by comparing the strength of metal binding to a protein versus the strength of binding to competing sites inside cells.

Cancer Influences the Elemental Composition of the Myocardium More Strongly than Conjugated Linoleic Acids-Chemometric Approach to Cardio-Oncological Studies.

The aim of the study was to verify in a cardio-oncological model experiment if conjugated linoleic acids (CLA) fed to rats with mammary tumors affect the content of selected macro- and microelements in their myocardium. The diet of Sprague-Dawley females was supplemented either with CLA isomers or with safflower oil. In hearts of rats suffering from breast cancer, selected elements were analyzed with a quadrupole mass spectrometer with inductively coupled plasma ionization (ICP-MS). In order to better understand the data trends, cluster analysis, principal component analysis and linear discriminant analysis were applied. Mammary tumors influenced macro- and microelements content in the myocardium to a greater extent than applied diet supplementation. Significant influences of diet (p = 0.0192), mammary tumors (p = 0.0200) and interactions of both factors (p = 0.0151) were documented in terms of Fe content. CLA significantly decreased the contents of Cu and Mn (p = 0.0158 and p = 0.0265, respectively). The level of Ni was significantly higher (p = 0.0073), which was more pronounced in groups supplemented with CLA. The obtained results confirmed antioxidant properties of CLA and the relationship with Se deposition. Chemometric techniques distinctly showed that the coexisting pathological process induced differences to the greater extent than diet supplementation in the elemental content in the myocardium, which may impinge on cardiac tissue's susceptibility to injuries.

Role of metal complexation on the solubility and enzymatic hydrolysis of phytate.

Phytate is a dominant form of organic phosphorus (P) in the environment. Complexation and precipitation with polyvalent metal ions can stabilize phytate, thereby significantly hinder the hydrolysis by enzymes. Here, we studied the stability and hydrolyzability of environmentally relevant metal phytate complexes (Na, Ca, Mg, Cu, Zn, Al, Fe, Al/Fe, Mn, and Cd) under different pHs, presence of metal chelators, and thermal conditions. Our results show that the order of solubility of metal phytate complexes is as follows: i) for metal species: Na, Ca, Mg > Cu, Zn, Mn, Cd > Al, Fe, ii) under different pHs: pH 5.0 > pH 7.5), and iii) in the presence of chelators: EDTA> citric acid. Phytate-metal complexes are mostly resistant towards acid hydrolysis (except Al-phytate), and dry complexes are generally stable at high pressure and temperature under autoclave conditions (except Ca phytate). Inhibition of metal complex towards enzymatic hydrolysis by Aspergillus niger phytase was variable but found to be highest in Fe phytate complex. Strong chelating agents such as EDTA are insufficient for releasing metals from the complexes unless the reduction of metals (such as Fe) occurs first. The insights gained from this research are expected to contribute to the current understanding of the fate of phytate in the presence of various metals that are commonly present in agricultural soils.

Pressure-driven accumulation of Mn-doped mesoporous silica nanoparticles containing 5-aza-2-deoxycytidine and docetaxel at tumours with a dry cupping device.

Drug delivery with the help of nanoparticles could transport more payloads to tumour site. Owing to their limited accumulation and penetration in the tumour tissues, to increase delivery efficiency is currently still required for applying nanomedicine to treat tumour. Here, we initially report a pressure-driven accumulation of drug-loaded nanoparticles to tumours for efficient tumour therapy with a dry cupping device. The mesoporous Mn-doped silica based nanoparticles delivering 5-aza-2-deoxycytidine and docetaxel were prepared, characterised and used as a model nanomedicine to investigate the potential of dry cupping treatment. For this system, the Mn doping not only endowed the mesoporous silica nanoparticles biodegradability, but also made it much easier to bind a tumour targeting group, which is a G-quadruplex-forming aptamer AS1411. On tumour-bearing mice, the in vivo results demonstrated that the dry cupping treatment could substantially improve the distribution of nanomedicines at tumour site, resulting in enhanced treatment efficacy. Overall, this method enables the therapeutical nanoparticles accumulate to tumour through increasing the blood perfusion as well as altering the biological barrier, which opened up possibilities for the development of pressure-driven nanomedicine accumulation at tumour site.

NIR Light-Propelled Janus-Based Nanoplatform for Cytosolic-Fueled microRNA Imaging.

Various nanoplatforms have been developed to visualize intracellular microRNAs (miRNAs) because of their clinical significance in tumor progression and diagnosis. However, the diffusion-limited motion of the nanoplatforms penalizes the miRNA imaging efficiency in cells. Herein, we fabricated a near-infrared (NIR) light-propelled Janus-based nanoplatform to advance the imaging response. The Janus nanomotor covered with an Au half-shell was loaded by the endocytosis adjuvant of the MnO2 nanosheet for delivering a miRNA-responsive hQN (hairpin DNA quadrangular nanostructure) probe with a catalyzed hairpin assembly (CHA). Once the nanoplatform entered into cells, the MnO2 nanosheet was degraded to Mn2+ by endogenous fuels (such as glutathione) to release the hQN probe. The NIR light irradiation of the nanoplatform generated a heat gradient and thus propelled motion of the nanoplatform. This process accelerated the intracellular reaction of the hQN probe with miRNAs to trigger the cascade CHA amplification with an enhanced fluorescence readout.

CO release from Mn(i)-based photoCORMs with single photons in the phototherapeutic region.

Both the instrumentation required for two photon excitation (TPE) and tissue damage possibility by high intensity laser lights could impede TPE-induced CO delivery in hospital settings. Herein we report two Mn(i)-based photoCORMs with a fac-{Mn(CO)3} moiety that exhibit facile CO release upon simple exposure to light within the phototherapeutic region (no TPE required).

Zinc, manganese, and copper amino acid complexes improve performance and bone characteristics of layer-type chicks under thermoneutral and cold stress conditions.

Two experiments were designed to evaluate the effect of mineral-amino acid complexes (AACM) as a partial replacement of inorganic mineral (IM) in layer-type chicks' diets. Both studies had the same dietary treatments, where in experiment 1 (Exp. 1) was conducted under thermoneutral conditions from 0 to 35 D and chicks in experiment 2 (Exp. 2) were exposed to cold stress conditions at nighttime during the first 15 D and to thermoneutral condition from 16 to 35 D. For each trial, 1,200 one-day-old Lohmann Brown chicks were used, with 20 cage replicates with 30 chicks per cage. Treatments consisted of the control diet (IM; with 70, 70, and 8 mg/kg of zinc [Zn], manganese [Mn], and copper [Cu], respectively) and the treatment diet (AACM, with 40, 40, and 2.75 mg/kg of Zn, Mn, and Cu, respectively, from IM sources, along with 30, 30, and 5.25 mg/kg of Zn, Mn, and Cu, respectively). Data were submitted to analysis of variance, and means were compared using the t-test (P < 0.05). In Exp. 1, there were no significant differences between treatments on chick performance. However, AACM-fed chicks had higher thymus (P = 0.03) and cecum weight (P < 0.01), superior micromineral deposition in the tibias (P < 0.01), and reduced phosphorus excretion (P = 0.03). In Exp. 2, chicks fed with AACM had higher body weight gain (P = 0.04), better average daily feed intake (P = 0.03), lower phosphorus excretion (P = 0.02), and higher liver and pancreas weight (P < 0.01) in the last week of the study. In conclusion, chicks fed with AACM under thermoneutral conditions had higher bone mineralization and reduced excretion of phosphorus, and in adverse conditions, AACM improves performance and liver and pancreas weight, also reducing phosphorus excretion.

Targeted Manganese doped silica nano GSH-cleaner for treatment of Liver Cancer by destroying the intracellular redox homeostasis.

Background: Glutathione (GSH), the primary antioxidant in cells, could fight against oxidative stress. Tumor cells display a higher GSH level than normal cells for coping with the hyperoxidative state, which meets the requirements of enhanced metabolism and vicious proliferation. Therefore, the consumption of GSH will lead to cell redox imbalance and impede life activities. Herein, targeted sorafenib (SFB) loaded manganese doped silica nanoparticle (FaPEG-MnMSN@SFB) was constructed, which could destroy the intracellular redox homeostasis by consuming GSH. Methods: In this study, MnMSN was prepared by an optimized one-pot Stober's method for loading SFB, and FaPEG chain was modified on the surface of MnMSN to achieve long circulation and targeted delivery. The anticancer efficacy and mechanism of the designed FaPEG-MnMSN@SFB were assessed both in vitro and in vivo.Results: FaPEG-MnMSN@SFB exhibited efficient antitumor activity by dual depleting intracellular GSH (the degradation of MnMSN would consume intracellular GSH and the SFB would inhibit the effect of Xc- transport system to inhibit GSH synthesis). Moreover, disruption of redox balance would lead to apoptosis and reactive oxygen species (ROS)-dependent ferroptosis of tumor cells. Conclusion: Such a GSH-starvation therapeutic strategy would cause multi-path programmed cell death and could be a promising strategy for cancer therapy.

Biodegradable pH-responsive amorphous calcium carbonate nanoparticles as immunoadjuvants for multimodal imaging and enhanced photoimmunotherapy.

Development of bioresponsive theranostic nanoparticles to enhance cancer diagnostics and control cancer metastasis is highly desirable. In this study, we developed such a bioresponsive theranostic nanoparticle for synergistic photoimmunotherapy. In particular, these nanoparticles were constructed by embedding indocyanine green (ICG) into Mn2+-doped amorphous calcium carbonate (ACC(Mn)) nanoparticles, followed by loading of the Toll-like-receptor-7 agonist imiquimod (IMQ). The IMQ@ACC(Mn)-ICG/PEG nanoparticles respond to the acidic pH of the tumor microenvironment (TME) and co-deliver ICG and IMQ into the tumor. Selective phototherapy was achieved upon activation using a near-infrared laser. In the presence of IMQ and arising from phototherapeutically treated tumor cells, tumor-associated antigens give rise to a strong antitumor immune response. Reversal of the immunosuppressive TME via H+ scavenging of the tumor through ACC nanoparticles effectively inhibits tumor metastases. Moreover, the combination of ICG and Mn2+ also serves as an advanced contrast agent for cancer multimode imaging. Overall, these bioresponsive nanoparticles provide a promising approach for cancer theranostics with promising potential for future clinical translation.

Traces matter: Targeted optimization of monoclonal antibody N-glycosylation based on/by implementing automated high-throughput trace element screening.

The use of high-throughput systems in cell culture process optimization offers various opportunities in biopharmaceutical process development. Here we describe the potential for acceleration and enhancement of product quality optimization and de novo bioprocess design regarding monoclonal antibody N-glycosylation by using an iterative statistical Design of Experiments (DoE) strategy based on our automated microtiter plate-based system for suspension cell culture. In our example, the combination of an initial screening of trace metal building blocks with a comprehensive DoE-based screening of 13 different trace elemental ions at three concentration levels in one run revealed most effective levers for N-glycan processing and biomass formation. Obtained results served to evaluate optimal concentration ranges and the right supplementation timing of relevant trace elements at shake flask and 2 L bioreactor scale. This setup identified manganese, copper, zinc, and iron as major factors. Manganese and copper acted as inverse key players in N-glycosylation, showing a positive effect of manganese and a negative effect of copper on glycan maturation in a zinc-dependent manner. Zinc and iron similarly improved cell growth and biomass formation. These findings allowed determining optimal concentration ranges for all four trace elements to establish control on desired product quality attributes regarding premature afucosylated and mature galactosylated glycan species. Our results demonstrates the power of combining robotics with DoE screening to enhance product quality optimization and to improve process understanding, thus, enabling targeted product quality control.

Methacrylated gellan gum and hyaluronic acid hydrogel blends for image-guided neurointerventions.

Cell-based therapies delivered via intrathecal injection are considered as one of the most promising solutions for the treatment of amyotrophic lateral sclerosis (ALS). Herein, injectable manganese-based biocompatible hydrogel blends were developed, that can allow image-guided cell delivery. The hydrogels can also provide physical support for cells during injection, and at the intrathecal space after transplantation, while assuring cell survival. In this regard, different formulations of methacrylated gellan gum/hyaluronic acid hydrogel blends (GG-MA/HA) were considered as a vehicle for cell delivery. The hydrogels blends were supplemented with paramagnetic Mn2+ to allow a real-time monitorization of hydrogel deposition via T1-weighted magnetic resonance imaging (MRI). The developed hydrogels were easily extruded and formed a stable fiber upon injection into the cerebrospinal fluid. Hydrogels prepared with a 75 : 25 GG-MA to HA ratio supplemented with MnCl2 at 0.1 mM showed controlled hydrogel degradation, suitable permeability, and a distinct MRI signal in vitro and in vivo. Additionally, human-derived adipose stem cells encapsulated in 75 : 25 GG-MA/HA hydrogels remained viable for up to 14 days of culture in vitro. Therefore, the engineered hydrogels can be an excellent tool for injectable image-guided cell delivery approaches.