Bacteria-Based Backpacks to Enhance Adoptive Macrophage Transfer against Solid Tumors.

Adoptive cell therapy has emerged as a promising approach for cancer treatment. However, the transfer of macrophages exhibits limited efficacy against solid tumors due to the dynamic cellular phenotypic shift from antitumor to protumor states within the immunosuppressive tumor microenvironment. In this study, a strategy of attaching bacteria to macrophages (Mø@bac) is reported that endows adoptively infused macrophages with durable stimulation by leveraging the intrinsic immunogenicity of bacteria. These attached bacteria, referred to as backpacks, are encapsulated with adhesive nanocoatings and can sustainably control the cellular phenotypes in vivo. Moreover, Mø@bac can repolarize endogenous tumor-associated macrophages, leading to a more robust immune response and thus reducing the tumor progression in a murine 4T1 cancer model without any side effects. This study utilizing bacteria as cellular backpacks opens a new avenue for the development of cell therapies.

Rapid and facile preparation of NiFe-layered double hydroxide nanosheets as self-supported electrode for glucose detection in drink sample.

Layered double hydroxides have been widely used for electrochemical glucose detection due to their layered structure with more active sites, but they suffer from lower electrical conductivity and long-time hydrothermal preparation. In this paper, NiFe-layered double hydroxide nanosheets supported on nickel foam (NiFe-LDH NSs/NF) was prepared using an ultrafast and facile method via in-situ corroding foam nickel in FeCl3 solution under room temperature, and the whole synthetic process can be accomplished within several minutes. The as-fabricated NiFe-LDH NSs/NF shows significant catalytic activity in the glucose oxidation, showing its great promise in glucose detection. As a self-supported electrode, NiFe-LDH NSs/NF is favorable for glucose detection, with a sensitivity of 9.79 and 3.29 mA mM-1 cm-2 within the linear range of 0.001 to 1.16 mM and 1.16 to 4.67 mM, respectively. Moreover, NiFe-LDH NSs/NF is also selective and reliable towards glucose detection in drink sample.

A PD-L1-targeting Regulator for Metabolic Reprogramming to Enhance Glutamine Inhibition-Mediated Synergistic Antitumor Metabolic and Immune Therapy.

Inhibition of glutamine metabolism in tumor cells can cause metabolic compensation-mediated glycolysis enhancement and PD-L1 upregulation-induced immune evasion, significantly limiting the therapeutic efficacy of glutamine inhibitors. Here, inspired by the specific binding of receptor and ligand, a PD-L1-targeting metabolism and immune regulator (PMIR) are constructed by decorating the glutaminase inhibitor (BPTES)-loading zeolitic imidazolate framework (ZIF) with PD-L1-targeting peptides for regulating the metabolism within the tumor microenvironment (TME) to improve immunotherapy. At tumor sites, PMIR inhibits glutamine metabolism of tumor cells for elevating glutamine levels within the TME to improve the function of immune cells. Ingeniously, the accompanying PD-L1 upregulation on tumor cells causes self-amplifying accumulation of PMIR through PD-L1 targeting, while also blocking PD-L1, which has the effects of converting enemies into friends. Meanwhile, PMIR exactly offsets the compensatory glycolysis, while disrupting the redox homeostasis in tumor cells via the cooperation of components of the ZIF and BPTES. These together cause immunogenic cell death of tumor cells and relieve PD-L1-mediated immune evasion, further reshaping the immunosuppressive TME and evoking robust immune responses to effectively suppress bilateral tumor progression and metastasis. This work proposes a rational strategy to surmount the obstacles in glutamine inhibition for boosting existing clinical treatments.

Dendritic Cell-Based In Situ Nanovaccine for Reprogramming Lipid Metabolism to Boost Tumor Immunotherapy.

Cancer vaccines have been considered to be an alternative therapeutic strategy for tumor therapy in the past decade. However, the popularity and efficacy of cancer vaccines were hampered by tumor antigen heterogeneity and the impaired function of cross-presentation in the tumor-infiltrating dendritic cells (TIDCs). To overcome these challenges, we engineered an in situ nanovaccine (named as TPOP) based on lipid metabolism-regulating and innate immune-stimulated nanoparticles. TPOP could capture tumor antigens and induce specific recognition by TIDCs to be taken up. Meanwhile, TPOP could manipulate TIDC lipid metabolism and inhibit de novo synthesis of fatty acids, thus improving the ability of TIDCs to cross-present by reducing their lipid accumulation. Significantly, intratumoral injection of TPOP combined with pretreatment with doxorubicin showed a considerable therapeutic effect in the subcutaneous mouse colorectal cancer model and melanoma model. Moreover, in combination with immune checkpoint inhibitors, such TPOP could markedly inhibit the growth of distant tumors by systemic antitumor immune responses. This work provides a safe and promising strategy for improving the function of immune cells by manipulating their metabolism and activating the immune system effectively for in situ cancer vaccines.

Engineering metal-based hydrogel-mediated tertiary lymphoid structure formation via activation of the STING pathway for enhanced immunotherapy.

Tertiary lymphoid structures (TLSs) primarily constructed by multiple immune cells can effectively enhance tumor immune responses, but expediting the formation of TLSs is still an enormous challenge. Herein, a stimulator of interferon gene (STING)-activating hydrogel (ZCCG) was elaborately developed by coordinating Zn2+ with 4,5-imidazole dicarboxylic acid, and simultaneously integrating chitosan (a stimulant of STING pathway activation) and CpG (an agonist of toll-like receptor 9, TLR9) for initiating and activating cGAS-STING and TLR9 pathway-mediated immunotherapy. Moreover, the dual-pathway activation could effectively enhance the infiltration of immune cells and the expression of lymphocyte-recruiting chemokines in the tumor microenvironment (TME), thereby promoting the formation of TLSs and further strengthening tumoricidal immunity. Local administration of the hydrogel could prime systemic immune responses and long-term immune memory and improve the therapeutic effects of programmed death-1 antibody (αPD-1) to inhibit tumor progression, metastasis and recurrence. The engineered hydrogel lays the foundation for tumor immunotherapy strategies based on the enhanced formation of TLSs via the activation of the cGAS-STING and TLR9 pathways.

Damage analysis and mechanism study of sol-gel coating over KDP crystal under multi-pulse of laser irradiation at low flux.

The purpose of this study is to analyze the damage of antireflective (AR) coating over potassium dihydrogen phosphate (KDP) crystal subjected to multi-pulse laser irradiation at low flux under vacuum. Fresh silica AR was characterized as a reference; Atomic Force Microscope (AFM), Scanning Electron Microscopy (SEM), profilometer, and Scanning Near-Field Optical Microscope Photo-induced Force Microscope (SNOM-PiFM) were employed to analyze the characteristics of coatings. The experimental results indicated that the damage of AR coating over the KDP crystal was mainly caused by partial exfoliation, which exposed silica particles beneath the surface. It was found that the accumulated tensile stress led to coating damage with the increase of laser pulse. The initial coating damage was observed to extend and interconnect to form large-area exfoliation. Splitting mechanism of SiO-Si TO3 was observed at vibration mode peaks of 1064 cm-1 and 1096 cm-1showing progressing irradiation damage. Based on this study, it would be helpful to suppress the damage probability of AR coating over KDP crystal applied in high-power laser systems. Moreover, the applicability of SNOM-PiFM method to study the Infrared Radiation (IR) spectra of ultra-thin coatings with transparent substrates was proposed.

Progress of engineered bacteria for tumor therapy.

Recently, with the rapid development of bioengineering technology and nanotechnology, natural bacteria were modified to change their physiological activities and therapeutic functions for improved therapeutic efficiency of diseases. These engineered bacteria were equipped to achieve directed genetic reprogramming, selective functional reorganization and precise spatio-temporal control. In this review, research progress in the basic modification methodologies of engineered bacteria were summarized, and representative researches about their therapeutic performances for tumor treatment were illustrated. Moreover, the strategies for the construction of engineered colonies based on engineering of individual bacteria were summarized, providing innovative ideas for complex functions and efficient anti-tumor treatment. Finally, current limitation and challenges of tumor therapy utilizing engineered bacteria were discussed.

Atomically thin van der Waals tunnel field-effect transistors and its potential for applications.

Power dissipation is a crucial problem as the packing density of transistors increases in modern integrated circuits. Tunnel field-effect transistors (TFETs), which have high energy filtering provided by band-to-band tunneling (BTBT), have been proposed as an alternative electronics architecture to decrease the energy loss in bias operation and to achieve steep switching at room temperature. Very recently, the BTBT behavior has been demonstrated in van der Waals heterostructures by using unintentionally doped semiconductors. The reason of the BTBT formation is attributed to a significant band bending near the heterointerface, resulting in carrier accumulations. In this work, to investigate charge transport in type-III transistors, we adopted the same band-bending concept to fabricate van der Waals BP/MoS2 heterostructures. Through analyzing the temperature dependence of their electrical properties, we carefully ruled out the contribution of metal-semiconductor contact resistances and improved our understanding of carrier injection in 2D type-III transistors. The BP/MoS2 heterostructures showed both negative differential resistance and 1/f 2 current fluctuations, strongly demonstrating the BTBT operation. Finally, we also designed a TFET based on this heterostructure with an ionic liquid gate, and this TFET demonstrated an subthreshold slope can successfully surmount the thermal limit of 60 mV/decade. This work improves our understanding of charge transport in such layered heterostructures and helps to improve the energy efficiency of next-generation nanoscale electronics.