TRMT13 inhibits the growth of papillary thyroid cancer by targeting ANAPC4.

The recently discovered gene TRMT13 encodes a type of RNA methylase and is a member of the CCDC family (also called CCDC76). Here, we delineate its role in papillary thyroid cancer (PTC). Bioinformatics analysis shows significant TRMT13 and ANAPC4 downregulation in PTC and reveals that the expression levels of both genes are linearly correlated. Subsequent analyses confirm that both TRMT13 and ANAPC4 expressions are downregulated in PTC tissues and that this change in expression has a significant impact on cancer diagnosis. We conduct assays on PTC cells subjected to TRMT13 and ANAPC4 silencing or overexpression to assess the biological effects of these genes. We also perform rescue experiments to validate the regulatory effects of TRMT13 on ANAPC4. A nude mouse tumor model is used to evaluate the effects of TRMT13 and ANAPC4 on PTC tumorigenesis. TRMT13 expression is decreased in PTC tissues and cell lines and is positively correlated with that of ANAPC4. Cell assays reveal that TRMT13/ANAPC4 attenuates the malignancy of PTC cells by restraining cell proliferation, migration and invasion, while rescue experiments corroborate that ANAPC4 is a downstream target of TRMT13. In the nude mouse xenograft model, both TRMT13 and ANAPC4 inhibit tumor growth, and TRMT13 and ANAPC4 expression levels are significantly associated with survival. Taken together, these findings lead to the conclusion that TRMT13 inhibits PTC growth via ANAPC4, indicating a new role of TRMT13 and providing insights into the tRNA methyltransferase and coiled-coil domain-containing protein families.

Structural insights into the unusual core photocomplex from a triply extremophilic purple bacterium, Halorhodospira halochloris.

Halorhodospira (Hlr.) halochloris is a triply extremophilic phototrophic purple sulfur bacterium, as it is thermophilic, alkaliphilic, and extremely halophilic. The light-harvesting-reaction center (LH1-RC) core complex of this bacterium displays an LH1-Qy transition at 1,016 nm, which is the lowest-energy wavelength absorption among all known phototrophs. Here we report the cryo-EM structure of the LH1-RC at 2.42 Å resolution. The LH1 complex forms a tricyclic ring structure composed of 16 αßγ-polypeptides and one αß-heterodimer around the RC. From the cryo-EM density map, two previously unrecognized integral membrane proteins, referred to as protein G and protein Q, were identified. Both of these proteins are single transmembrane-spanning helices located between the LH1 ring and the RC L-subunit and are absent from the LH1-RC complexes of all other purple bacteria of which the structures have been determined so far. Besides bacteriochlorophyll b molecules (B1020) located on the periplasmic side of the Hlr. halochloris membrane, there are also two arrays of bacteriochlorophyll b molecules (B800 and B820) located on the cytoplasmic side. Only a single copy of a carotenoid (lycopene) was resolved in the Hlr. halochloris LH1-α3ß3 and this was positioned within the complex. The potential quinone channel should be the space between the LH1-α3ß3 that accommodates the single lycopene but does not contain a γ-polypeptide, B800 and B820. Our results provide a structural explanation for the unusual Qy red shift and carotenoid absorption in the Hlr. halochloris spectrum and reveal new insights into photosynthetic mechanisms employed by a species that thrives under the harshest conditions of any phototrophic microorganism known.

New insights on the photocomplex of Roseiflexus castenholzii revealed from comparisons of native and carotenoid-depleted complexes.

In wild-type phototrophic organisms, carotenoids (Crts) are primarily packed into specific pigment-protein complexes along with (Bacterio)chlorophylls and play important roles in the photosynthesis. Diphenylamine (DPA) inhibits carotenogenesis but not phototrophic growth of anoxygenic phototrophs and eliminates virtually all Crts from photocomplexes. To investigate the effect of Crts on assembly of the reaction center-light-harvesting (RC-LH) complex from the filamentous anoxygenic phototroph Roseiflexus (Rfl.) castenholzii, we generated carotenoidless (Crt-less) RC-LH complexes by growing cells in the presence of DPA. Here, we present cryo-EM structures of the Rfl. castenholzii native and Crt-less RC-LH complexes with resolutions of 2.86 Å and 2.85 Å, respectively. From the high-quality map obtained, several important but previously unresolved details in the Rfl. castenholzii RC-LH structure were determined unambiguously including the assignment and likely function of three small polypeptides, and the content and spatial arrangement of Crts with bacteriochlorophyll molecules. The overall structures of Crt-containing and Crt-less complexes are similar. However, structural comparisons showed that only five Crts remain in complexes from DPA-treated cells and that the subunit X (TMx) flanked on the N-terminal helix of the Cyt-subunit is missing. Based on these results, the function of Crts in the assembly of the Rfl. castenholzii RC-LH complex and the molecular mechanism of quinone exchange is discussed. These structural details provide a fresh look at the photosynthetic apparatus of an evolutionary ancient phototroph as well as new insights into the importance of Crts for proper assembly and functioning of the RC-LH complex.

Multifunctional Protein Hybrid Nanoplatform for Synergetic Photodynamic-Chemotherapy of Malignant Carcinoma by Homologous Targeting Combined with Oxygen Transport.

Photodynamic therapy (PDT) under hypoxic conditions and drug resistance in chemotherapy are perplexing problems in anti-tumor treatment. In addition, central nervous system neoplasm-targeted nanoplatforms are urgently required. To address these issues, a new multi-functional protein hybrid nanoplatform is designed, consisting of transferrin (TFR) as the multicategory solid tumor recognizer and hemoglobin for oxygen supply (ODP-TH). This protein hybrid framework encapsulates the photosensitizer protoporphyrin IX (PpIX) and chemotherapeutic agent doxorubicin (Dox), which are attached by a glutathione-responsive disulfide bond. Mechanistically, ODP-TH crosses the blood-brain barrier (BBB) and specifically aggregated in hypoxic tumors via protein homology recognition. Oxygen and encapsulated drugs ultimately promote a therapeutic effect by down-regulating the abundance of multidrug resistance gene 1 (MDR1) and hypoxia-inducible factor-1-α (HIF-1α). The results reveal that ODP-TH achieves oxygen transport and protein homology recognition in the hypoxic tumor occupation. Indeed, compared with traditional photodynamic chemotherapy, ODP-TH achieves a more efficient tumor-inhibiting effect. This study not only overcomes the hypoxia-related inhibition in combination therapy by targeted oxygen transport but also achieves an effective treatment of multiple tumors, such as breast cancer and glioma, providing a new concept for the construction of a promising multi-functional targeted and intensive anti-tumor nanoplatform.

Homotypic Targeted Photosensitive Nanointerferer for Tumor Cell Cycle Arrest to Boost Tumor Photoimmunotherapy.

Recent advances in tumor immunotherapy mainly tend to remodel the immunosuppressive tumor microenvironment (TME) for immune enhancement. However, the complexity of TME makes it unlikely to achieve satisfactory therapeutic effects with any single intervention alone. Here, we focus on exposing intrinsic features of tumor cells to trigger direct pleiotropic antitumor immunity. We develop a photosensitive nanointerferer that is engineered with a nanoscale metal-organic framework decorated with tumor cell membranes for targeted delivery of a photosensitizer and small interfering RNA, which is used to knock down cyclin-dependent kinase 4 (Cdk4). Cdk4 blockade can arrest the cell cycle of tumor cells to facilitate antigen exposure and increase the expression level of programmed cell death protein ligand 1 (PD-L1). Under laser irradiation, photodynamic damage triggered by the nanointerferer induces the release of tumor antigens and recruitment of dendritic cells (DCs), thereby promoting the antitumor activity of CD8+ T cells in combination with anti-PD-L1 antibodies. Ultimately, these events markedly retard tumor progression in a mouse model of ectopic colon tumor with negligible adverse effects. This study provides an alternative treatment for effective antitumor immunity by exciting the intrinsic potential of tumor cells to initiate immune responses while reducing immune-related toxicities.

Perfluorooctanoic acid triggers oxidative stress in anaerobic digestion of sewage sludge.

Perfluorooctanoic acid (PFOA), as a recalcitrant organic pollutant, inevitably enters wastewater treatment facilities and is enriched in settled sludge. However, the potential impact of PFOA on sludge treatment has never been documented. In this study, the effect of PFOA on anaerobic digestion of sewage sludge and its underlying mechanism were investigated through batch and long-term experiments. The presence of PFOA was found to be deleterious for methane production from sewage sludge. 170 mg/kg total solids PFOA reduced the cumulative methane production from 197.1 ± 1.92-159.9 ± 3.10 mL/g volatile solids. PFOA induces the production of reactive oxygen species, which directly leads to cell inactivation and interferes with methane production. PFOA stimulates microorganisms to secrete more extracellular polymeric substances (mainly proteins), which not only hinders the solubilization of organic matter but also down-regulate enzyme activities to inhibit acidification and methanogenesis. In addition, PFOA reduces the diversity of microorganisms, especially the abundance of acid-producing bacteria and methanogens, making the microbial community unfavorable for methane production.

Advances in nanomaterials for treatment of hypoxic tumor.

The hypoxic tumor microenvironment is characterized by disordered vasculature and rapid proliferation of tumors, resulting from tumor invasion, progression and metastasis. The hypoxic conditions restrict efficiency of tumor therapies, such as chemotherapy, radiotherapy, phototherapy and immunotherapy, leading to serious results of tumor recurrence and high mortality. Recently, research has concentrated on developing functional nanomaterials to treat hypoxic tumors. In this review, we categorize such nanomaterials into (i) nanomaterials that elevate oxygen levels in tumors for enhanced oxygen-dependent tumor therapy and (ii) nanomaterials with diminished oxygen dependence for hypoxic tumor therapy. To elevate oxygen levels in tumors, oxygen-carrying nanomaterials, oxygen-generating nanomaterials and oxygen-economizing nanomaterials can be used. To diminish oxygen dependence of nanomaterials for hypoxic tumor therapy, therapeutic gas-generating nanomaterials and radical-generating nanomaterials can be used. The biocompatibility and therapeutic efficacy of these nanomaterials are discussed.

Hybrid Vesicles Based on Autologous Tumor Cell Membrane and Bacterial Outer Membrane To Enhance Innate Immune Response and Personalized Tumor Immunotherapy.

Tumor heterogeneity, often leading to metastasis, limits the development of tumor therapy. Personalized therapy is promising to address tumor heterogeneity. Here, a vesicle system was designed to enhance innate immune response and amplify personalized immunotherapy. Briefly, the bacterial outer membrane vesicle (OMV) was hybridized with the cell membrane originated from the tumor (mT) to form new functional vesicles (mTOMV). In vitro experiments revealed that the mTOMV strengthened the activation of innate immune cells and increased the specific lysis ability of T cells in homogeneous tumors. In vivo experiments showed that the mTOMV effectively accumulated in inguinal lymph nodes, then inhibited lung metastasis. Besides, the mTOMV evoked adaptive immune response in homologous tumor rather than the heterogeneous tumor, reversibly demonstrating the effects of personalized immunotherapy. The functions to inhibit tumor growth and metastasis accompanying good biocompatibility and simple preparation procedure of mTOMV provide their great potential for clinical applications.

A near infrared ratiometric platform based π-extended porphyrin metal-organic framework for O2 imaging and cancer therapy.

Photodynamic therapy (PDT) is widely researched in tumor treatment, but its therapeutic effect is affected by oxygen (O2) concentration of tumor site. Here, we developed a Pd-coordinated π-conjugated extended porphyrin doped porphyrin metal-organic-framework (named as PTP). PTP can achieve near infrared (NIR) O2 concentration ratiometric imaging, solving the problems of short detection wavelengths and influence of self-concentrations. With the NIR excitation wavelength and the ability of higher singlet oxygen (1O2) generation, PTP can induce PDT more effectively. The efficient PDT also mediates cancer immunogenic cell death (ICD), which combines with the immune checkpoint inhibitor αPD-1 to achieve obviously cancer suppression and anti-metastasis effect. This theranostic NIR ratiometric nanoprobe can be used as a pre-evaluation on the outcome of PDT and high-efficient cancer combined treatment system, which will find great potential in tumor diagnosis and treatment.

Astaxanthin attenuates acute cerebral infarction via Nrf-2/HO-1 pathway in rats.

OBJECTIVE: Acute cerebral infarction (ACI) is susceptible to cause disability or death of people. Astaxanthin (ATX) possesses the protective effect of organ injury. Therefore, the study was to explore the potential mechanism of protective effect with ATX on ACI. METHODS: 30 SD rats were divided into Sham, ACI, and ATX groups. The rats in the ATX group were pretreated with ATX by gavage for three days before surgery, while the rats in the other two groups were pretreated with saline. The model of ACI was established by thread embolization. 24 h after the operation, the neurological function was scored, and cerebral infarct area and pathological morphology of brains were measured; the edema of the brain was detected by dry/wet method; Western blot was applied to measure the translocation of Nrf-2 and the protein expression of HO-1, Bax and BCL-2; Brain cell apoptosis was assessed through TUNEL; ELISA was used to detect the oxidative stress factors of catalase (CAT) superoxide dismutase (SOD), glutathione peroxidase (GPX) and malondialdehyde (MDA), and the inflammatory factors of TNF-α, IL-1ß, IL-6. RESULT: Compared with the ACI group, ATX pretreatment can significantly improve neurological function; reduce the edema index of the brain, cerebral infarct area, cerebral pathological damage and apoptosis of brain cells. Moreover, ATX also can increase the protein expression of nuclear Nrf-2, HO-1, BCL-2, CAT, SOD, and GPX by decreasing the content of TNF-α, IL-1ß, IL-6, MDA, Bax and cytosolic Nrf-2. CONCLUSION: ATX might have a protective effect of acute cerebral infarction, and the mechanism is probably associated with suppressing oxidative stress, inflammation, and apoptosis by activating Nrf-2/HO-1signalling.

Monitoring the nitrous oxide emissions and biological nutrient removal from wastewater treatment: Impact of perfluorooctanoic acid.

The impacts of perfluorooctanoic acid (PFOA) on biological nutrient removal and nitrous oxide (N2O) emissions have been specifically studied. The experimental results show that PFOA inhibited nitrification, but promoted denitrification and reduced N2O emissions without significantly affecting phosphorus removal. The existence of 20 mg/L of PFOA increased total nitrogen removal efficiency from 78.7 ± 6.89 % to 86.8 ± 6.39 % and reduced N2O emission factor from 6.02 ± 0.24 % to 4.43 ± 0.10 %. The mechanism studies reveal that microorganisms released extracellular polymeric substances (EPS) under PFOA exposure to protect sludge cells against PFOA toxicity. The generated PFOA-EPS conjugates reduced the nitrification rate, but increased the denitrification rate by regulating the activity of oxidoreductases. In addition, PFOA reduced the activity of polyphosphate accumulating organisms and glycogen accumulating organisms to save carbon source for denitrification, which reduced the electronic competition between reductases, thereby achieving complete denitrification and N2O mitigation. The promotion of PFOA for denitrification and N2O mitigation can gain a more comprehensive cognition of the role of PFOA in wastewater treatment. The release mechanism of EPS can afford new insights for the development of effective methods to enhance nitrogen removal and reduce N2O emissions.

Analysis of the expression, function, prognosis and co-expression genes of DDX20 in gastric cancer.

DDX20 (DEAD-box polypeptide 20) is implicated in many cellular processes involving alteration of RNA secondary structure. The role of DDX20 in gastric cancer is still unknown. In the research, the expression of DDX20 and the functional roles of DDX20 in gastric cancer were detected. The increased DDX20 expression in gastric cancer tissue compared with normal gastric tissue was observed. Functional experiments indicated that DDX20 promoted gastric cancer MGC-803 and AGS cells growth, migration, and invasion in vitro. Surprisingly, survival analysis showed that high expression of DDX20 is a favorable prognostic factor for patients with gastric cancer. In addition, enrichment analysis revealed that there is a positive correlation between DDX20 expression and T cell activation in gastric cancer. but not in normal gastric tissues. Furthermore, we found that DDX20 expression level has significant positive correlations with activated CD8 + T cells and activated CD4 + T cells in gastric cancer. Therefore, we hypothesize that the prognostic role of DDX20 in gastric cancer patients may be due to patients with high DDX20 expression contained better immune activation. Taken together, these findings suggest that DDX20 can promote the progression of gastric cancer in vitro and its prognostic value in gastric cancer may be related to many factors, including immune activation.

Near-Infrared Light Responsive Nanoreactor for Simultaneous Tumor Photothermal Therapy and Carbon Monoxide-Mediated Anti-Inflammation.

Photothermal therapy (PTT) is an effective treatment modality with high selectivity for tumor suppression. However, the inflammatory responses caused by PTT may lead to adverse reactions including tumor recurrence and therapeutic resistance, which are regarded as major problems for PTT. Here, a near-infrared (NIR) light-responsive nanoreactor (P@DW/BC) is fabricated to simultaneously realize tumor PTT and carbon monoxide (CO)-mediated anti-inflammatory therapy. Defective tungsten oxide (WO3) nanosheets (DW NSs) are decorated with bicarbonate (BC) via ferric ion-mediated coordination and then modified with polyethylene glycol (PEG) on the surface to fabricate PEG@DW/BC or P@DW/BC nanosheets. Upon 808 nm NIR laser irradiation, the DW content in P@DW/BC can serve as not only a photothermal agent to realize photothermal conversion but also a photocatalyst to convert carbon dioxide (CO2) to CO. In particular, the generated heat can also trigger the decomposition of BC to produce CO2 near the NSs, thus enhancing the photocatalytic CO generation. Benefiting from the efficient hyperthermia and CO generation under single NIR laser irradiation, P@DW/BC can realize effective thermal ablation of tumor and simultaneous inhibition of PTT-induced inflammation.

Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA­374a/forkhead box O1 signaling axis.

Ovarian cancer is a prominent disease that demonstrates high incidence rates in women and often presents multidrug resistance. Propofol has been demonstrated to suppress the malignancy of various types of human cancer; however, the underlying molecular mechanisms of propofol in ovarian cancer remain largely unknown. The present study aimed to investigate whether and how propofol inhibits proliferation and cisplatin (DDP) resistance in ovarian cancer cells. Ovarian cancer cell viability was assessed by the Cell Counting kit­8 assay; apoptosis and cell cycle progression were determined by flow cytometry; the relative expression levels of microRNA (miR)­374a and forkhead box O1 (FOXO1) were analyzed using reverse transcription­quantitative PCR; the binding ability of miR­374a to FOXO1 was assessed by the dual­luciferase reporter assay; cellular sensitivity to DDP was detected using the MTT assay; and finally, the protein expression levels of FOXO1, p27, and Bcl­2­like­protein 11 (Bim) were analyzed by western blotting. Propofol reduced viability, promoted apoptosis and decreased miR­374a expression levels in A2780 cells. In addition, the viability of A2780/DDP cells in the propofol + DDP treatment group was significantly inhibited, and the apoptotic rate was increased. In addition, miR­374a overexpression increased cell viability and the proportion of cells in the S phase, and decreased the proportion of cells in the G0/G1 phase. Conversely, genetic knockdown of miR­374a exerted the opposite effects on cell viability and cell cycle progression. Moreover, miR­374a was demonstrated to bind to FOXO1. Propofol promoted the expression of FOXO1, p27 and Bim, induced cell cycle arrest and decreased ovarian cancer cell viability. In addition, treatment with propofol and DDP regulated FOXO1 and increased apoptosis of ovarian cancer cells. In conclusion, propofol downregulated miR­374a and modulated the FOXO1 pathway to reduce proliferation and DDP resistance in ovarian cancer cells.

A MSN-based tumor-targeted nanoplatform to interfere with lactate metabolism to induce tumor cell acidosis for tumor suppression and anti-metastasis.

Lactate, the main contributor to the acidic tumor microenvironment, not only promotes the proliferation of tumor cells, but also closely relates to tumor invasion and metastasis. Here, a tumor targeting nanoplatform, designated as Me&Flu@MSN@MnO2-FA, was fabricated for effective tumor suppression and anti-metastasis by interfering with lactate metabolism of tumor cells. Metformin (Me) and fluvastatin sodium (Flu) were incorporated into MnO2-coated mesoporous silicon nanoparticles (MSNs), the synergism between Me and Flu can modulate the pyruvate metabolic pathway to produce more lactate, and concurrently inhibit lactate efflux to induce intracellular acidosis to kill tumor cells. As a result of the restricted lactate efflux, the extracellular lactate concentration is reduced, and the ability of the tumor cells to migrate is also weakened. This ingenious strategy based on Me&Flu@MSN@MnO2-FA showed an obvious inhibitory effect on tumor growth and resistance to metastasis.

Remodeling extracellular matrix based on functional covalent organic framework to enhance tumor photodynamic therapy.

Photodynamic therapy (PDT) is a promising treatment modality for tumor suppression. However, the hypoxic state of most solid tumors might largely hinder the efficacy of PDT. Here, a functional covalent organic framework (COF) is fabricated to enhance PDT efficacy by remodeling the tumor extracellular matrix (ECM). Anti-fibrotic drug pirfenidone (PFD) is loaded in an imine-based COF (COFTTA-DHTA) and followed by the decoration of poly(lactic-co-glycolic-acid)-poly(ethylene glycol) (PLGA-PEG) to fabricate PFD@COFTTA-DHTA@PLGA-PEG, or PCPP. After injected intravenously, PCPP can accumulate and release PFD in tumor sites, leading to down-regulation of ECM compenents such as hyaluronic acid (HA) and collagen I. Such depletion of tumor ECM reduces the intratumoral solid stress, a compressive force exerted by the ECM and cells, decompresses tumor blood vessels, and increases the density of effective vascular areas, resulting in significantly improved oxygen supply in tumor. Furthermore, PCPP-mediated tumor ECM depletion also enhances the tumor uptake of subsequently injected Protoporphyrinl IX (PPIX)-conjugated peptide formed nanomicelles (NM-PPIX) due to the improved enhanced permeability and retention (EPR) effect. Both the alleviated tumor hypoxia and improved tumor homing of photosensitizer (PS) molecules after PCPP treatment significantly increase the reactive oxygen species (ROS) generation in tumor and therefore realize greatly enhanced PDT effect of tumor in vivo.

Bacteria-Instructed In Situ Aggregation of AuNPs with Enhanced Photoacoustic Signal for Bacterial Infection Bioimaging.

The emergence of drug-resistant bacteria is becoming the focus of global public health. Early-stage pathogen bioimaging will offer a unique perspective to obtain infection information in patients. A photoacoustic (PA) contrast agent based on functional peptide modified gold nanoparticles (AuNPs@P1) is developed. These nanoparticles can be specifically tailored surface peptides by bacterial overexpressed enzyme inducing in situ aggregation of the gold nanoparticles. In the meantime, the close aggregation based on the hydrogen bonding, π-π stacking, and hydrophobic interaction of the peptide residues on the surface of gold nanoparticles exhibits a typical redshifted and broadened plasmon band. In addition, this active targeting and following in situ stimuli-induced aggregation contribute to increased nanoparticle accumulation in the infected site. Finally, the dynamic aggregation of AuNPs@P1 results in dramatically enhanced photoacoustic signals for bioimaging bacterial infection in vivo with high sensitivity and specificity. It is envisioned that this PA contrast agent may provide a new approach for early detection of bacterial infection in vivo.

Intra/Extracellular Lactic Acid Exhaustion for Synergistic Metabolic Therapy and Immunotherapy of Tumors.

Regulating the tumor microenvironment (TME) has been a promising strategy to improve antitumor therapy. Here, a red blood cell membrane (mRBC)-camouflaged hollow MnO2 (HMnO2 ) catalytic nanosystem embedded with lactate oxidase (LOX) and a glycolysis inhibitor (denoted as PMLR) is constructed for intra/extracellular lactic acid exhaustion as well as synergistic metabolic therapy and immunotherapy of tumor. Benefiting from the long-circulation property of the mRBC, the nanosystem can gradually accumulate in a tumor site through the enhanced permeability and retention (EPR) effect. The extracellular nanosystem consumes lactic acid in the TME by catalyzing its oxidation reaction via LOX. Meanwhile, the intracellular nanosystem releases the glycolysis inhibitor to cut off the source of lactic acid, as well as achieve antitumor metabolic therapy through the blockade of the adenosine triphosphate (ATP) supply. Both the extracellular and intracellular processes can be sensitized by O2 , which can be produced during the decomposition of endogenous H2 O2 catalyzed by the PMLR nanosystem. The results show that the PMLR nanosystem can ceaselessly remove lactic acid, and then lead to an immunocompetent TME. Moreover, this TME regulation strategy can effectively improve the antitumor effect of anti-PDL1 therapy without the employment of any immune agonists to avoid the autoimmunity.

Artificial Natural Killer Cells for Specific Tumor Inhibition and Renegade Macrophage Re-Education.

Natural killer (NK) cells can not only recognize and eliminate abnormal cells but also recruit and re-educate immune cells to protect the host. However, the functions of NK cells are often limited in the immunosuppressive tumor microenvironment (TME). Here, artificial NK cells (designated as aNK) with minor limitations of TME for specific tumor killing and renegade macrophage re-education are created. The red blood cell membrane (RBCM) cloaks perfluorohexane (PFC) and glucose oxidase (GOX) to construct the aNK. The aNK can directly kill tumor cells by exhausting glucose and generating hydrogen peroxide (H2 O2 ). The generated H2 O2 is also similar to cytokines and chemokines for recruiting immune cells and re-educating survived macrophages to attack tumor cells. In addition, the oxygen-carried PFC can strengthen the catalytic reaction of GOX and normalize the hypoxic TME. In vitro and in vivo experiments display that aNK with slight TME limitations exhibit efficient tumor inhibition and immune activation. The aNK will provide a new sight to treat tumor as the supplement of aggressive NK cells.