Materials for Immunotherapy Shields, C. Wyatt; Wang, Lily Li‐Wen; Evans, Michael A. ...
Advanced materials (Weinheim),
04/2020, Volume:
32, Issue:
13
Journal Article
Peer reviewed
Breakthroughs in materials engineering have accelerated the progress of immunotherapy in preclinical studies. The interplay of chemistry and materials has resulted in improved loading, targeting, and ...release of immunomodulatory agents. An overview of the materials that are used to enable or improve the success of immunotherapies in preclinical studies is presented, from immunosuppressive to proinflammatory strategies, with particular emphasis on technologies poised for clinical translation. The materials are organized based on their characteristic length scale, whereby the enabling feature of each technology is organized by the structure of that material. For example, the mechanisms by which i) nanoscale materials can improve targeting and infiltration of immunomodulatory payloads into tissues and cells, ii) microscale materials can facilitate cell‐mediated transport and serve as artificial antigen‐presenting cells, and iii) macroscale materials can form the basis of artificial microenvironments to promote cell infiltration and reprogramming are discussed. As a step toward establishing a set of design rules for future immunotherapies, materials that intrinsically activate or suppress the immune system are reviewed. Finally, a brief outlook on the trajectory of these systems and how they may be improved to address unsolved challenges in cancer, infectious diseases, and autoimmunity is presented.
Immunotherapy has established a new paradigm for the management and treatment of diseases, leading to numerous clinical breakthroughs. The means by which materials have helped overcome critical barriers associated with emerging immunotherapies are reviewed, and new opportunities for their continued advancement are discussed.
Transition metal (TM)‐based bimetallic spinel oxides can efficiently activate peroxymonosulfate (PMS) presumably attributed to enhanced electron transfer between TMs, but the existing model cannot ...fully explain the efficient TM redox cycling. Here, we discover a critical role of TM−O covalency in governing the intrinsic catalytic activity of Co3−xMnxO4 spinel oxides. Experimental and theoretical analysis reveals that the Co sites significantly raises the Mn valence and enlarges Mn−O covalency in octahedral configuration, thereby lowering the charge transfer energy to favor MnOh–PMS interaction. With appropriate MnIV/MnIII ratio to balance PMS adsorption and MnIV reduction, the Co1.1Mn1.9O4 exhibits remarkable catalytic activities for PMS activation and pollutant degradation, outperforming all the reported TM spinel oxides. The improved understandings on the origins of spinel oxides activity for PMS activation may inspire the development of more active and robust metal oxide catalysts.
The Mn−O covalency was enlarged by the Co sites mainly in the octahedral configuration, which results in a decreased charge transfer energy to favor Mn–PMS interaction and enhance MnIV reduction to boost PMS activation activity of Co‐Mn spinel oxides.
Metal–organic frameworks (MOFs) hold great promise as porous matrixes for the incorporation of Au nanoparticles (NPs) because of their rationally designed framework structures. Unfortunately, the ...as‐synthesized bulk MOFs usually vary in the range of micrometer or sub‐micrometer size, rendering extremely longer molecular diffusion distance of chemical species. 2D MOF nanosheets with extended lateral dimensions and nanometer thickness are expected to implement fast kinetics and effectively lower mass‐transfer barriers during embedding Au NPs process and sequential catalytic reactions. In this study, a novel 2D nanosheet of mixed‐ligand Ni(II) MOF (referred to NMOF‐Ni) is successfully fabricated. With the merits of well‐defined micropores and functional oxygen‐decorated inner walls, the incorporation of quite monodisperse ultrasmall Au nanoparticles of around 1 nm into NMOF‐Ni has been achieved for the first time. The resulting nanocomposites exhibit remarkable catalytic performance and good size selectivity toward aqueous reduction reactions of nitrophenol, taking advantage of ultrasmall Au and 2D nanosheet nature, as well as the intact microporosity of host matrix. The present encouraging findings might shed light on new ways to develop high‐performance heterogeneous catalysts by using of 2D MOF nanosheets with functional cavities as hosts for homogeneous distribution of ultrasmall Au NPs.
Ultrasmall Au nanoparticles are successfully dispersed into a novel 2D nanosheet of mixed‐ligand Ni(II) metal–organic frameworks. The as‐obtained nanocomposites not only exhibit prominent catalytic activity with excellent recyclability, but also show good size selectivity toward aqueous reduction reactions of nitrophenol, by virtue of ultrasmall Au and 2D nanosheet nature, as well as the intact microporosity of host matrix.
Hard carbon attracts considerable attention as an anode material for sodium‐ion batteries; however, their poor rate capability and low realistic capacity have motivated intense research effort toward ...exploiting nanostructured carbons in order to boost their comprehensive performance. Ultramicropores are considered essential for attaining high‐rate capacity as well as initial Coulombic efficiency by allowing the rapid diffusion of Na+ and inhibiting the contact of the electrolyte with the inner carbon surfaces. Herein, hard carbon nanosheets with centralized ultramicropores (≈0.5 nm) and easily accessible carbonyl groups (CO)/hydroxy groups (OH) are synthesized via interfacial assembly and carbonization strategies, delivering a large capacity (318 mA h g−1 at 0.02 A g−1), superior rate capability (145 mA h g−1 at 5.00 A g−1), and approximately 95% of reversible capacity below 1.00 V. Notably, a new charge model favoring fast capacitive sodium storage with dual potential plateaus is proposed. That is, the deintercalation of Na+ from graphitic layers is manifested as the low‐potential plateau region (0.01−0.10 V), contributing to stable insertion capacity; meanwhile, the surface desodiation process of the CO and OH groups corresponds to the high‐potential plateau region (0.40−0.70 V), contributing to a fast capacitive storage.
Hard carbon nanosheets with centralized ultramicropores (≈0.5 nm), accessible functional CO/OH groups, and large graphitic layer spacings exhibit excellent sodium‐storage properties. The desodiation process from graphitic layers and CO/OH groups results in a new sodium‐storage characteristic with dual‐potential plateaus during the charge process, which favors a high output of 95%, realistic capacity, and rapidly capacitive sodium storage.
The gut microbiota is a complex community of bacteria residing in the intestine. Animal models have demonstrated that several factors contribute to and can significantly alter the composition of the ...gut microbiota, including genetics; the mode of delivery at birth; the method of infant feeding; the use of medications, especially antibiotics; and the diet. There may exist a gut microbiota signature that promotes intestinal inflammation and subsequent systemic low-grade inflammation, which in turn promotes the development of type 2 diabetes. There are preliminary studies that suggest that the consumption of probiotic bacteria such as those found in yogurt and other fermented milk products can beneficially alter the composition of the gut microbiome, which in turn changes the host metabolism. Obesity, insulin resistance, fatty liver disease, and low-grade peripheral inflammation are more prevalent in patients with low α diversity in the gut microbiome than they are in patients with high α diversity. Fermented milk products, such as yogurt, deliver a large number of lactic acid bacteria to the gastrointestinal tract. They may modify the intestinal environment, including inhibiting lipopolysaccharide production and increasing the tight junctions of gut epithelia cells.
Summary
Various lineages of ammonia‐oxidizing archaea (AOA) are present in deep waters, but the mechanisms that determine ecotype formation are obscure. We studied 18 high‐quality genomes of the ...marine group I AOA lineages (alpha, gamma and delta) from the Mariana and Ogasawara trenches. The genomes of alpha AOA resembled each other, while those of gamma and delta lineages were more divergent and had even undergone insertion of some phage genes. The instability of the gamma and delta AOA genomes could be partially due to the loss of DNA polymerase B (polB) and methyladenine DNA glycosylase (tag) genes responsible for the repair of point mutations. The alpha AOA genomes harbour genes encoding a thrombospondin‐like outer membrane structure that probably serves as a barrier to gene flow. Moreover, the gamma and alpha AOA lineages rely on vitamin B12‐independent MetE and B12‐dependent MetH, respectively, for methionine synthesis. The delta AOA genome contains genes involved in uptake of sugar and peptide perhaps for heterotrophic lifestyle. Our study provides insights into co‐occurrence of cladogenesis and anagenesis in the formation of AOA ecotypes that perform differently in nitrogen and carbon cycling in dark oceans.
A Mn‐electrocatalytic ring‐opening azidation of tert‐cyclobutanols has been developed. The regioselective method is applicable for the azidation of a diverse array of cyclobutanols to provide ...practical γ‐azido ketones in 23–91% yields under chemical oxidants‐free reaction conditions. Detailed mechanistic studies suggest the process of Mn‐mediated alkoxy radical generation followed by β‐scission to form carbon‐centered radical species is possibly involved in this transformation.
The precise recognition and sensing of steroids, a type of vital biomolecules, hold immense practical value across various domains. In this study, we introduced corral4BINOLs (C4BINOLs), a pair of ...enantiomeric conjugated deep‐cavity hosts, as novel synthetic receptors for binding steroids. Due to the strong hydrophobic effect of their deep nonpolar, chiral cavities, the two enantiomers of C4BINOLs demonstrated exceptionally high recognition affinities (up to 1012 M−1) for 16 important steroidal compounds as well as good enantioselectiviy (up to 15.5) in aqueous solutions, establishing them as the most potent known steroid receptors. Harnessing their ultrahigh affinity, remarkable enantioselectivity, and fluorescence emission properties, the two C4BINOL enantiomers were employed to compose a fluorescent sensor array which achieved discrimination and sensing of 16 structurally similar steroids at low concentrations.
A pair of enantiomeric macrocycles, RRRR‐ and SSSS‐C4BINOL, demonstrated exceptionally high recognition affinities (up to 1012 M−1) towards 16 important steroidal compounds in aqueous solutions, establishing them the most effective known steroid receptors. The two C4BINOL enantiomers were employed to compose a fluorescent sensor array which achieved discrimination and sensing of 16 structurally similar steroids in biofluids.
Many protein‐coding oncofetal genes are highly expressed in murine and human fetal liver and silenced in adult liver. The protein products of these hepatic oncofetal genes have been used as clinical ...markers for the recurrence of hepatocellular carcinoma (HCC) and as therapeutic targets for HCC. Herein we examined the expression profiles of long noncoding RNAs (lncRNAs) found in fetal and adult liver in mice. Many fetal hepatic lncRNAs were identified; one of these, lncRNA‐mPvt1, is an oncofetal RNA that was found to promote cell proliferation, cell cycling, and the expression of stem cell‐like properties of murine cells. Interestingly, we found that human lncRNA‐hPVT1 was up‐regulated in HCC tissues and that patients with higher lncRNA‐hPVT1 expression had a poor clinical prognosis. The protumorigenic effects of lncRNA‐hPVT1 on cell proliferation, cell cycling, and stem cell‐like properties of HCC cells were confirmed both in vitro and in vivo by gain‐of‐function and loss‐of‐function experiments. Moreover, mRNA expression profile data showed that lncRNA‐hPVT1 up‐regulated a series of cell cycle genes in SMMC‐7721 cells. By RNA pulldown and mass spectrum experiments, we identified NOP2 as an RNA‐binding protein that binds to lncRNA‐hPVT1. We confirmed that lncRNA‐hPVT1 up‐regulated NOP2 by enhancing the stability of NOP2 proteins and that lncRNA‐hPVT1 function depends on the presence of NOP2. Conclusion: Our study demonstrates that the expression of many lncRNAs is up‐regulated in early liver development and that the fetal liver can be used to search for new diagnostic markers for HCC. LncRNA‐hPVT1 promotes cell proliferation, cell cycling, and the acquisition of stem cell‐like properties in HCC cells by stabilizing NOP2 protein. Regulation of the lncRNA‐hPVT1/NOP2 pathway may have beneficial effects on the treatment of HCC. (Hepatology 2014;60:1278–1290)
Abstract
Context
The key gut microbial biomarkers for polycystic ovarian syndrome (PCOS) and how dysbiosis causes insulin resistance and PCOS remain unclear.
Objective
To assess the characteristics ...of intestinal flora in PCOS and explore whether abnormal intestinal flora can affect insulin resistance and promote PCOS and whether chenodeoxycholic acid (CDCA) can activate intestinal farnesoid X receptor (FXR), improving glucose metabolism in PCOS.
Setting and design
The intestinal flora of treatment-naïve PCOS patients and hormonally healthy controls was analyzed. Phenotype analysis, intestinal flora analysis, and global metabolomic profiling of caecal contents were performed on a letrozole-induced PCOS mouse model; similar analyses were conducted after 35 days of antibiotic treatment on the PCOS mouse model, and glucose tolerance testing was performed on the PCOS mouse model after a 35-day CDCA treatment. Mice receiving fecal microbiota transplants from PCOS patients or healthy controls were evaluated after 10 weeks.
Results
Bacteroides was significantly enriched in treatment-naïve PCOS patients. The enrichment in Bacteroides was reproduced in the PCOS mouse model. Gut microbiota removal ameliorated the PCOS phenotype and insulin resistance and increased relative FXR mRNA levels in the ileum and serum fibroblast growth factor 15 levels. PCOS stool-transplanted mice exhibited insulin resistance at 10 weeks but not PCOS. Treating the PCOS mouse model with CDCA improved glucose metabolism.
Conclusions
Bacteroides is a key microbial biomarker in PCOS and shows diagnostic value. Gut dysbiosis can cause insulin resistance. FXR activation might play a beneficial rather than detrimental role in glucose metabolism in PCOS.
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