Nanofactory for metabolic and chemodynamic therapy: pro-tumor lactate trapping and anti-tumor ROS transition

Lactate plays a critical role in tumorigenesis, invasion and metastasis. Exhausting lactate in tumors holds great promise for the reversal of the immunosuppressive tumor microenvironment (TME). Herein, we report on a “lactate treatment plant” (i.e., nanofactory) that can dynamically trap pro-tumor lactate and in situ transformation into anti-tumor cytotoxic reactive oxygen species (ROS) for a synergistic chemodynamic and metabolic therapy. To this end, lactate oxidase (LOX) was nano-packaged by cationic polyethyleneimine (PEI), assisted by a necessary amount of copper ions (PLNPCu). As a reservoir of LOX, the tailored system can actively trap lactate through the cationic PEI component to promote lactate degradation by two-fold efficiency. More importantly, the byproducts of lactate degradation, hydrogen peroxide (H2O2), can be transformed into anti-tumor ROS catalyzing by copper ions, mediating an immunogenic cell death (ICD). With the remission of immunosuppressive TME, ICD process effectively initiated the positive immune response in 4T1 tumor model (88% tumor inhibition). This work provides a novel strategy that rationally integrates metabolic therapy and chemodynamic therapy (CDT) for combating tumors. Graphical Abstract

Nanofactory for Metabolic and Chemodynamic Therapy: Pro-Tumor Lactate Trapping and Anti-Tumor ROS Transition

Lactate plays a critical role in tumorigenesis, invasion and metastasis. Exhausting lactate in tumors holds great promise for the reversal of the immunosuppressive tumor microenvironment (TME). Herein, we report on a “lactate treatment plant” (i.e., nanofactory) that can dynamically trap pro-tumor lactate and in situ transformation into anti-tumor cytotoxic reactive oxygen species (ROS) for a synergistic chemodynamic and metabolic therapy. To this end, lactate oxidase (LOX) was nano-packaged by cationic polyethyleneimine (PEI), assisted by a necessary amount of copper ions (PLNPCu). As a reservoir of LOX, the tailored system can actively trap lactate through the cationic PEI component to promote lactate degradation by two-fold efficiency. More importantly, the byproducts of lactate degradation, hydrogen peroxide (H2O2), can be transformed into anti-tumor ROS catalyzing by copper ions, mediating an immunogenic cell death (ICD). With the remission of immunosuppressive TME, ICD process effectively initiated the positive immune response in 4T1 tumor model (88% tumor inhibition). This work provides a novel strategy that rationally integrates metabolic therapy and chemodynamic therapy (CDT) for combating tumors.

Subgroup level differences of physiological activities in marine Lokiarchaeota

Asgard is a recently discovered archaeal superphylum, closely linked to the emergence of eukaryotes. Among Asgard archaea, Lokiarchaeota are abundant in marine sediments, but their in situ activities are largely unknown except for Candidatus ‘Prometheoarchaeum syntrophicum’. Here, we tracked the activity of Lokiarchaeota in incubations with Helgoland mud area sediments (North Sea) by stable isotope probing (SIP) with organic polymers, 13C-labelled inorganic carbon, fermentation intermediates and proteins. Within the active archaea, we detected members of the Lokiarchaeota class Loki-3, which appeared to mixotrophically participate in the degradation of lignin and humic acids while assimilating CO2, or heterotrophically used lactate. In contrast, members of the Lokiarchaeota class Loki-2 utilized protein and inorganic carbon, and degraded bacterial biomass formed in incubations. Metagenomic analysis revealed pathways for lactate degradation, and involvement in aromatic compound degradation in Loki-3, while the less globally distributed Loki-2 instead rely on protein degradation. We conclude that Lokiarchaeotal subgroups vary in their metabolic capabilities despite overlaps in their genomic equipment, and suggest that these subgroups occupy different ecologic niches in marine sediments.

Draft Genome Sequence of the Syntrophic Lactate-Degrading Bacterium Tepidanaerobacter syntrophicus JL T

We report here a high-quality draft genome sequence of the type strain (JL) of Tepidanaerobacter syntrophicus , an obligately anaerobic and moderately thermophilic bacterium, which is able to perform syntrophic lactate degradation with hydrogenotrophic methanogens. The genome comprises 2.43 Mb in 9 scaffolds, with a G+C content of 38.6%.

Desulfosoma caldarium gen. nov., sp. nov., a thermophilic sulfate-reducing bacterium from a terrestrial hot spring

A thermophilic, sulfate-reducing bacterium, designated strain USBA-053T, was isolated from a terrestrial hot spring located at a height of 2500 m in the Colombian Andes (5° 45′ 33.29″ N 73° 6′ 49.89″ W), Colombia. Cells of strain USBA-053T were oval- to rod-shaped, Gram-negative and motile by means of a single polar flagellum. The strain grew autotrophically with H2 as the electron donor and heterotrophically on formate, propionate, butyrate, valerate, isovalerate, lactate, pyruvate, ethanol, glycerol, serine and hexadecanoic acid in the presence of sulfate as the terminal electron acceptor. The main end products from lactate degradation, in the presence of sulfate, were acetate, CO2 and H2S. Strain USBA-053T fermented pyruvate in the absence of sulfate and grew optimally at 57 °C (growth temperature ranged from 50 °C to 62 °C) and pH 6.8 (growth pH ranged from 5.7 to 7.7). The novel strain was slightly halophilic and grew in NaCl concentrations ranging from 5 to 30 g l−1, with an optimum at 25 g l−1 NaCl. Sulfate, thiosulfate and sulfite were used as electron acceptors, but not elemental sulfur, nitrate or nitrite. The G+C content of the genomic DNA was 56±1 mol%. 16S rRNA gene sequence analysis indicated that strain USBA-053T was a member of the class Deltaproteobacteria, with Desulfacinum hydrothermale MT-96T as the closest relative (93 % gene sequence similarity). On the basis of physiological characteristics and phylogenetic analysis, it is suggested that strain USBA-053T represents a new genus and novel species for which the name Desulfosoma caldarium gen. nov., sp. nov. is proposed. The type strain of the type species is USBA-053T ( = KCTC 5670T = DSM 22027T).