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1.
Acta Biomater ; 180: 423-435, 2024 May.
Article in English | MEDLINE | ID: mdl-38641183

ABSTRACT

Communication between tumors and lymph nodes carries substantial significance for antitumor immunotherapy. Remodeling the immune microenvironment of tumor-draining lymph nodes (TdLN) plays a key role in enhancing the anti-tumor ability of immunotherapy. In this study, we constructed a biomimetic artificial lymph node structure composed of F127 hydrogel loading effector memory T (TEM) cells and PD-1 inhibitors (aPD-1). The biomimetic lymph nodes facilitate the delivery of TEM cells and aPD-1 to the TdLN and the tumor immune microenvironment, thus realizing effective and sustained anti-tumor immunotherapy. Exploiting their unique gel-forming and degradation properties, the cold tumors were speedily transformed into hot tumors via TEM cell supplementation. Meanwhile, the efficacy of aPD-1 was markedly elevated compared with conventional drug delivery methods. Our finding suggested that the development of F127@TEM@aPD-1 holds promising potential as a future novel clinical drug delivery technique. STATEMENT OF SIGNIFICANCE: F127@TEM@aPD-1 show unique advantages in cancer treatment. When injected subcutaneously, F127@TEM@aPD-1 can continuously supplement TEM cells and aPD-1 to tumor draining lymph nodes (TdLN) and the tumor microenvironment, not only improving the efficacy of ICB therapy through slow release, but also exhibiting dual regulatory effects on the tumor and TdLN.


Subject(s)
Delayed-Action Preparations , Hydrogels , Lymph Nodes , Memory T Cells , Programmed Cell Death 1 Receptor , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Lymph Nodes/drug effects , Lymph Nodes/pathology , Lymph Nodes/immunology , Mice , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Memory T Cells/drug effects , Memory T Cells/immunology , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/pharmacology , Delayed-Action Preparations/pharmacokinetics , Tumor Microenvironment/drug effects , Cell Line, Tumor , Immune Checkpoint Inhibitors/pharmacology , Immunotherapy/methods , Female , Mice, Inbred C57BL , Humans
2.
J Nanobiotechnology ; 22(1): 174, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38609922

ABSTRACT

Photothermal therapy is favored by cancer researchers due to its advantages such as controllable initiation, direct killing and immune promotion. However, the low enrichment efficiency of photosensitizer in tumor site and the limited effect of single use limits the further development of photothermal therapy. Herein, a photo-responsive multifunctional nanosystem was designed for cancer therapy, in which myeloid-derived suppressor cell (MDSC) membrane vesicle encapsulated decitabine-loaded black phosphorous (BP) nanosheets (BP@ Decitabine @MDSCs, named BDM). The BDM demonstrated excellent biosafety and biochemical characteristics, providing a suitable microenvironment for cancer cell killing. First, the BDM achieves the ability to be highly enriched at tumor sites by inheriting the ability of MDSCs to actively target tumor microenvironment. And then, BP nanosheets achieves hyperthermia and induces mitochondrial damage by its photothermal and photodynamic properties, which enhancing anti-tumor immunity mediated by immunogenic cell death (ICD). Meanwhile, intra-tumoral release of decitabine induced G2/M cell cycle arrest, further promoting tumor cell apoptosis. In vivo, the BMD showed significant inhibition of tumor growth with down-regulation of PCNA expression and increased expression of high mobility group B1 (HMGB1), calreticulin (CRT) and caspase 3. Flow cytometry revealed significantly decreased infiltration of MDSCs and M2-macrophages along with an increased proportion of CD4+, CD8+ T cells as well as CD103+ DCs, suggesting a potentiated anti-tumor immune response. In summary, BDM realizes photothermal therapy/photodynamic therapy synergized chemotherapy for cancer.


Subject(s)
Myeloid-Derived Suppressor Cells , Neoplasms , Photochemotherapy , Biomimetics , CD8-Positive T-Lymphocytes , Decitabine/pharmacology , Photothermal Therapy , Neoplasms/drug therapy
3.
Oral Dis ; 2024 Mar 10.
Article in English | MEDLINE | ID: mdl-38462885

ABSTRACT

OBJECTIVE: Ferroptosis has been defined as a novel form of regulated cell death characterized by iron-dependent lipid peroxidation. Manganese has been used to induce ferroptosis in cancer cells recently. This study aims to investigate whether manganese can induce ferroptosis in oral squamous cell carcinoma (OSCC) and the underlying biological mechanisms. MATERIALS AND METHODS: Cancer cells with or without manganese treatment were analyzed by RNA-sequencing to identify ferroptosis-related genes. Next, the activation of YAP/TAZ/ACSL4-ferroptosis signaling pathway was detected. Bioinformatic analysis and immunofluorescence assay were used to explore the phase separation of YAP/TAZ. Finally, specimens of OSCC patients were applied to analyze the clinical significance of YAP/TAZ/ACSL4. RESULTS: RNA-sequencing analysis showed the ferroptosis-related genes and YAP/TAZ were upregulated after manganese treatment. The results of immunofluorescence, ELISA, western blotting, etc. further confirmed that manganese-induced ferroptosis depends on YAP/TAZ/ACSL4 signaling pathway. Moreover, the activation of ACSL4 was achieved by YAP/TAZ phase separation. The survival analysis in OSCC specimen suggested that the higher level of YAP/TAZ-ACSL4 axis expression indicates longer survival. CONCLUSIONS: Manganese induces YAP/TAZ phase separation and subsequent ACSL4 activation via YAP/TAZ nuclear translocation, which facilitates ferroptosis of OSCC. Then YAP/TAZ-ACSL4 axis can be used as a potential prognostic predictor of OSCC patients.

4.
Bioact Mater ; 33: 532-544, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38162511

ABSTRACT

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

5.
Biofabrication ; 16(2)2024 01 31.
Article in English | MEDLINE | ID: mdl-38241709

ABSTRACT

The suitable microenvironment of bone regeneration is critically important for periodontitis-derived bone defect repair. Three major challenges in achieving a robust osteogenic reaction are the exist of oral inflammation, pathogenic bacteria invasion and unaffluent seed cells. Herein, a customizable and multifunctional 3D-printing module was designed with glycidyl methacrylate (GMA) modified epsilon-poly-L-lysine (EPLGMA) loading periodontal ligament stem cells (PDLSCs) and myeloid-derived suppressive cells membrane vesicles (MDSCs-MV) bioink (EPLGMA/PDLSCs/MDSCs-MVs, abbreviated as EPM) for periodontitis-derived bone defect repair. The EPM showed excellent mechanical properties and physicochemical characteristics, providing a suitable microenvironment for bone regeneration.In vitro, EPMs presented effectively kill the periodontopathic bacteria depend on the natural antibacterial properties of the EPL. Meanwhile, MDSCs-MV was confirmed to inhibit T cells through CD73/CD39/adenosine signal pathway, exerting an anti-inflammatory role. Additionally, seed cells of PDLSCs provide an adequate supply for osteoblasts. Moreover, MDSCs-MV could significantly enhance the mineralizing capacity of PDLSCs-derived osteoblast. In the periodontal bone defect rat model, the results of micro-CT and histological staining demonstrated that the EPM scaffold similarly had an excellent anti-inflammatory and bone regeneration efficacyin vivo. This biomimetic and multifunctional 3D-printing bioink opens new avenues for periodontitis-derived bone defect repair and future clinical application.


Subject(s)
Periodontitis , Rats , Animals , Periodontitis/therapy , Periodontitis/metabolism , Stem Cells/metabolism , Osteogenesis , Inflammation , Periodontal Ligament/metabolism , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/pharmacology , Cell Differentiation , Cells, Cultured
6.
Small ; 20(15): e2307164, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37997555

ABSTRACT

Nowadays, highly active and stable alkaline bifunctional electrocatalysts toward water electrolysis that can work at high current density (≥1000 mA cm-2) are urgently needed. Herein, Mn-doped RuO2 (MnxRu1-xO2) nanofibers (NFs) are constructed to achieve this object, presenting wonderful hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) performances with the overpotentials of only 269 and 461 mV at 1 A cm-2 in 1 m KOH solution, and remarkably stability under industrial demand with 1 A cm-2, significantly better than the benchmark Pt/C and commercial RuO2 electrocatalysts, respectively. More importantly, the assembled Mn0.05Ru0.95O2 NFs||Mn0.05Ru0.95O2 NFs electrolyzer toward overall water splitting reaches the current density of 10 mA cm-2 with a cell voltage of 1.52 V and also delivers an outstanding stability over 150 h of continuous operation, far surpassing commercial Pt/C||commercial RuO2, RuO2 NFs||RuO2 NFs and most previously reported exceptional electrolyzers. Theoretical calculations indicate that Mn-doping into RuO2 can significantly optimize the electronic structure and weaken the strength of O─H bond to achieve the near-zero hydrogen adsorption free energy (ΔGH*) value for HER, and can also effectively weaken the adsorption strength of intermediate O* at the relevant sites, achieving the higher OER catalytic activity, since the overlapping center of p-d orbitals is closer to the Fermi level.

7.
Nanoscale ; 16(1): 273-283, 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-38059271

ABSTRACT

Exploring highly efficient electrocatalysts for the oxygen evolution reaction (OER) is of great significance for hydrogen production through water splitting. By means of high-throughput density functional theory (DFT) calculations, we investigated the OER catalytic activity of a series of one-dimensional carbon nanotube (CNT)-based systems containing TMN4 or TMN3 functional units. Through the screening of 3d/4d/5d transition metals (TMs) from Group IVB to Group VIII, eight newly obtained TMNx@CNT (x = 3 and 4) systems were found to exhibit excellent OER activity, with very low overpotentials in the range 0.29-0.51 V, where the Co, Rh, Ir, Ti, Fe, and Ru atoms could be used as active sites. It was found that under the framework of TMN3@CNTs, the pre-adsorption of some species from water dissociation on the relevant TM sites (TM = Ti, Fe, and Ru) could lead to a high OER catalytic activity, which was different from the general situation where OER reactions directly occur on the clean surfaces of the remaining systems with Co/Rh/Ir metal centers. Moreover, the catalytic mechanisms were analyzed in detail. This work can be conducive to obtaining low-cost and high-performance OER single-atom electrocatalysts based on excellent CNT nanomaterials.

8.
Front Microbiol ; 14: 1253025, 2023.
Article in English | MEDLINE | ID: mdl-37954233

ABSTRACT

Cancer remains a significant global challenge, with an estimated 47% increase in cancer patients from 2020 to 2040. Increasing research has identified microorganism as a risk factor for cancer development. The oral cavity, second only to the colon, harbors more than 700 bacterial species and serves as a crucial microbial habitat. Although numerous epidemiological studies have reported associations between oral microorganisms and major systemic tumors, the relationship between oral microorganisms and cancers remains largely unclear. Current research primarily focuses on respiratory and digestive system tumors due to their anatomical proximity to the oral cavity. The relevant mechanism research mainly involves 47% dominant oral microbial population that can be cultured in vitro. However, further exploration is necessary to elucidate the mechanisms underlying the association between oral microbiota and tumors. This review systematically summarizes the reported correlations between oral microbiota and common cancers while also outlining potential mechanisms that may guide biological tumor treatment.

9.
Mol Oncol ; 2023 Sep 04.
Article in English | MEDLINE | ID: mdl-37666495

ABSTRACT

Bacteria are the causative agents of various infectious diseases; however, the anti-tumor effect of some bacterial species has attracted the attention of many scientists. The human oral cavity is inhabited by abundant and diverse bacterial communities and some of these bacterial communities could play a role in tumor suppression. Therefore, it is crucial to find oral bacterial species that show anti-tumor activity on oral cancers. In the present study, we found that a high abundance of Porphyromonas gingivalis, an anaerobic periodontal pathogen, in the tumor microenvironment (TME) was positively associated with the longer survival of patients with oral squamous cell carcinoma (OSCC). An in vitro assay confirmed that P. gingivalis accelerated the death of OSCC cells by inducing cell cycle arrest at the G2/M phase, thus exerting its anti-tumor effect. We also found that P. gingivalis significantly decreased tumor growth in a 4-nitroquinoline-1-oxide-induced in situ OSCC mouse model. The transcriptomics data demonstrated that P. gingivalis suppressed the biosynthesis of mucin O-glycan and other O-glycans, as well as the expression of chemokines. Validation experiments further confirmed the downregulation of mucin-1 (MUC1) and C-X-C motif chemokine 17 (CXCL17) expression by P. gingivalis treatment. Flow cytometry analysis showed that P. gingivalis successfully reversed the immunosuppressive TME, thereby suppressing OSCC growth. In summary, the findings of the present study indicated that the rational use of P. gingivalis could serve as a promising therapeutic strategy for OSCC.

10.
Sci Adv ; 9(24): eadg3277, 2023 06 16.
Article in English | MEDLINE | ID: mdl-37315135

ABSTRACT

Dexamethasone (DEX) is the first drug to show life-saving efficacy in patients with severe coronavirus disease 2019 (COVID-19), while DEX is associated with serious adverse effects. Here, we report an inhaled, Self-immunoregulatory, Extracellular Nanovesicle-based Delivery (iSEND) system by engineering neutrophil nanovesicles with cholesterols to deliver DEX for enhanced treatment of COVID-19. Relying on surface chemokine and cytokine receptors, the iSEND showed improved targeting to macrophages and neutralized broad-spectrum cytokines. The nanoDEX, made by encapsulating DEX with the iSEND, efficiently promoted the anti-inflammation effect of DEX in an acute pneumonia mouse model and suppressed DEX-induced bone density reduction in an osteoporosis rat model. Relative to an intravenous administration of DEX at 0.1 milligram per kilogram, a 10-fold lower dose of nanoDEX administered by inhalation produced even better effects against lung inflammation and injury in severe acute respiratory syndrome coronavirus 2-challenged nonhuman primates. Our work presents a safe and robust inhalation delivery platform for COVID-19 and other respiratory diseases.


Subject(s)
COVID-19 , Nanoparticles , Mice , Rats , Animals , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/etiology , COVID-19 Drug Treatment , Dexamethasone/pharmacology , Dexamethasone/therapeutic use , Primates
11.
Molecules ; 28(9)2023 May 05.
Article in English | MEDLINE | ID: mdl-37175298

ABSTRACT

Based on the DFT calculations, two-dimensional (2D) R-graphyne has been demonstrated to have high stability and good conductivity, which can be conducive to the relevant electrocatalytic activity of the material. Different from the poor graphene, R-graphyne, which is completely composed of anti-aromatic structural units, can exhibit certain HER catalytic activity. In addition, doping the TM atoms in Group VIIIB can be considered an effective strategy to enhance the HER catalytic activity of R-graphyne. Particularly, Fe@R-graphyne, Os@R-graphyne, Rh@R-graphyne and Ir@R-graphyne can exhibit higher HER catalytic activities due to the formation of more active sites. Usually, the shorter the distance between the TM and C atoms is, the better the HER activity of the C-site is. Furthermore, doping Ni and Rh atoms of Group VIIIB can significantly improve the OER catalytic performance of R-graphyne. It can be found that ΔGO* can be used as a good descriptor for the OER activities of TM@R-graphyne systems. Both Rh@R-graphyne and Ni@R-graphyne systems can exhibit bifunctional electrocatalytic activities for HER/OER. In addition, all the relevant catalytic mechanisms are analyzed in detail. This work not only provides nonprecious and highly efficient HER/OER electrocatalysts, but also provides new ideas for the design of carbon-based electrocatalysts.

12.
Pharmaceutics ; 15(4)2023 Apr 10.
Article in English | MEDLINE | ID: mdl-37111686

ABSTRACT

Today, about 50% of men and 15-30% of women are estimated to face hair-related problems, which create a significant psychological burden. Conventional treatments, including drug therapy and transplantation, remain the main strategies for the clinical management of these problems. However, these treatments are hindered by challenges such as drug-induced adverse effects and poor drug penetration due to the skin's barrier. Therefore, various efforts have been undertaken to enhance drug permeation based on the mechanisms of hair regrowth. Notably, understanding the delivery and diffusion of topically administered drugs is essential in hair loss research. This review focuses on the advancement of transdermal strategies for hair regrowth, particularly those involving external stimulation and regeneration (topical administration) as well as microneedles (transdermal delivery). Furthermore, it also describes the natural products that have become alternative agents to prevent hair loss. In addition, given that skin visualization is necessary for hair regrowth as it provides information on drug localization within the skin's structure, this review also discusses skin visualization strategies. Finally, it details the relevant patents and clinical trials in these areas. Together, this review highlights the innovative strategies for skin visualization and hair regrowth, aiming to provide novel ideas to researchers studying hair regrowth in the future.

13.
J Colloid Interface Sci ; 640: 405-414, 2023 Jun 15.
Article in English | MEDLINE | ID: mdl-36867937

ABSTRACT

High-throughput DFT calculations are performed to explore the oxygen evolution reaction (OER) catalytic activity of a series of 2D graphene-based systems with TMO3 or TMO4 functional units. By screening the 3d/4d/5d transition metal (TM) atoms, a total of twelve TMO3@G or TMO4@G systems had extremely low overpotential of 0.33 âˆ¼ 0.59 V, in which the V/Nb/Ta atom in VB group and Ru/Co/Rh/Ir atom in VIII group served as the active sites. The mechanism analysis reveals that the filling of outer electrons of TM atom can play an important role in determining the overpotential value by affecting the ΔGO* value as an effective descriptor. Especially, in addition to the general situation of OER on the clean surface of the systems containing the Rh/Ir metal centers, the self-optimization process of TM-sites was carried out, and it made most of these single-atom catalysts (SAC) systems to have high OER catalytic activity. All these fascinating findings can contribute to an in-depth understanding of the OER catalytic activity and mechanism of the excellent graphene-based SAC systems. This work will facilitate the design and implementation of non-precious and highly efficient OER catalysts in the near future.

14.
Sci Technol Adv Mater ; 24(1): 2156257, 2023.
Article in English | MEDLINE | ID: mdl-36632346

ABSTRACT

Oral disease, as a class of diseases with very high morbidity, brings great physical and mental damage to people worldwide. The increasing burden and strain on individuals and society make oral diseases an urgent global health problem. Since the treatment of almost all oral diseases relies on materials, the rapid development of advanced materials and technologies has also promoted innovations in the treatment methods and strategies of oral diseases. In this review, we systematically summarized the application strategies in advanced materials and technologies for oral diseases according to the etiology of the diseases and the comparison of new and old materials. Finally, the challenges and directions of future development for advanced materials and technologies in the treatment of oral diseases were refined. This review will guide the fundamental research and clinical translation of oral diseases for practitioners of oral medicine.

15.
J Clin Med ; 12(2)2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36675491

ABSTRACT

As a typical hallmark of solid tumors, hypoxia affects the effects of tumor radiotherapy, chemotherapy, and photodynamic therapy. Therefore, targeting the hypoxic tumor microenvironment (TME) is a promising treatment strategy for cancer therapy. Here, we prepared an Albumin Human Serum (HSA)-coated perfluorocarbon (PFC) carrying oxygen (PFC@O2) to minimize OSCC hypoxia. The results showed that PFC@O2 significantly downregulated the expression of HIF-1α and the number of M2-like macrophages in vitro. Furthermore, PFC@O2 effectively inhibited the growth of oral squamous cell carcinoma (OSCC) and reduced the proportion of negative immunoregulatory cells, including myeloid-derived suppressor cells (MDSCs) and M2-like macrophages of TME in a 4-nitroquinoline N-oxide (4NQO)-induced mouse model. Conversely, the infiltration of CD4+ and CD8+ T cells was significantly increased in TME, suggesting that the anti-tumor immune response was enhanced. However, we also found that hypoxia-relative genes expression was positively correlated with CD68+/CD163+ TAMs in human tissue specimens. In summary, PFC@O2 could effectively inhibit the progression of OSCC by alleviating hypoxia, which provides a practical basis for gas therapy and gas synergistic therapy for OSCC.

16.
J Control Release ; 353: 752-766, 2023 01.
Article in English | MEDLINE | ID: mdl-36526020

ABSTRACT

The combination of excessive reactive oxygen species (ROS) levels, neuroinflammation, and pathogenic protein aggregation disrupt the homeostasis of brain microenvironment, creating conditions conducive to the progression of Parkinson's disease (PD). Restoring homeostasis by remodeling the brain microenvironment could reverse this complex pathological progression. However, treatment strategies that can induce this effect are currently unavailable. Herein, we developed a "Swiss Army Knife" nanodelivery platform consisting of matrine (MT) and polyethylene glycol-modified black phosphorus nanosheets (BP) that enables PD treatment by restoring brain microenvironment homeostasis. Under NIR irradiation, the photothermal effect induced by BP allowed the nanomedicine to cross the blood-brain barrier (BBB) and entered the brain parenchyma. In PD brains, the biological effects of BP and MT resulted in the removal of excess ROS, effective reduction of neuroinflammation, decreased aggregation of pathogenic proteins, and improved neurotransmitter delivery, eventually restoring dopamine levels in the striatum. This study demonstrated the effective capacity of a BP-based nanodelivery platform to enter the brain parenchyma and trigger multiple neuropathological changes in PD brains. The platform serves as a safe and effective anti-PD nanomedicine with immense clinical potential.


Subject(s)
Parkinson Disease , Phosphorus , Humans , Reactive Oxygen Species , Neuroinflammatory Diseases , Brain/metabolism , Parkinson Disease/drug therapy , Parkinson Disease/metabolism , Antiparkinson Agents/therapeutic use
17.
Cancer Immunol Immunother ; 72(5): 1315-1326, 2023 May.
Article in English | MEDLINE | ID: mdl-36436019

ABSTRACT

Myeloid-derived suppressor cells (MDSCs) are one of the tumor-infiltrating immune cell population, which play a powerful role in inhibiting anti-tumor immune response. Our previous studies have shown that STAT3 blockade can decrease the number of MDSCs in tumor microenvironment. However, it is unclear for the molecular mechanism of down-regulation MDSCs with STAT3 inhibitor. In this study, we first detected and analyzed the expression of p-STAT3, CD33, CD14, CD39 and CD73 via oral squamous cell carcinoma (OSCC) tissue array. We found that p-STAT3 was positively correlated with CD14, CD33, CD39, and CD73 in OSCC patient specimens. Then we found STAT3 blockade with S3I-201 reduced the expression of CD39/CD73 and the synthesis of adenosine, as well as inhibiting monocytes to MDSCs differentiation in vitro. Furthermore, we found that S3I-201 displayed prominent anti-tumor efficacy in C3H/He OSCC mouse model via inhibiting CD39/CD73-adenosine signal pathway and decreasing MDSCs. These results suggest that STAT3 signal can induce the differentiation of monocytes into MDSCs in tumor microenvironment depending on CD39/CD73-adenosine signal pathway and STAT3 blockade is a promising therapeutic strategy for OSCC.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Myeloid-Derived Suppressor Cells , Animals , Mice , Adenosine/pharmacology , Adenosine/metabolism , Carcinoma, Squamous Cell/metabolism , Cell Differentiation , Head and Neck Neoplasms/metabolism , Mice, Inbred C3H , Monocytes/metabolism , Mouth Neoplasms/pathology , Signal Transduction , Squamous Cell Carcinoma of Head and Neck/metabolism , Tumor Microenvironment , 5'-Nucleotidase/metabolism
18.
Oral Dis ; 29(3): 933-941, 2023 Apr.
Article in English | MEDLINE | ID: mdl-34773344

ABSTRACT

Accumulated evidence indicates that immune cell populations play pivotal roles in the process of tumor initiation, progression, recurrence, metastasis, and immune escape. Ferroptosis is a form of regulating cell death in the nexus between metabolism, redox biology, and human health. Ferroptosis is considered as a vital important event in HNSCC, but the underling mechanism of regulating immune cell populations remains poorly understood. Our tissue microarray study showed that patients with high expression of GPX4 were related to poor survival. Moreover, the expression of GPX4 has been negatively associated with immunogenic cell death-related protein calreticulin in HNSCC tissue cohort. Further, RSL3 was used to induce ferroptosis in HNSCC xenograft of C3H/He mouse. We found that the occurrence of ferroptosis had significantly reduced the number of myeloid-derived suppressor cells (MDSCs) and tumor-associated M2-like macrophages (M2 TAMs) in tumor microenvironment. Meanwhile, the tumor-infiltrating CD4+ and CD8+ T cells were increased. And the calreticulin and HMGB1 may be potential candidate proteins improving the immunosuppressive tumor microenvironment. Taken together, our project suggests that ferroptosis can promote anti-tumor immune response by reversing immunosuppressive microenvironment, indicating that ferroptosis inducer is a promising therapeutic strategy in HNSCC.


Subject(s)
Ferroptosis , Head and Neck Neoplasms , Humans , Mice , Animals , Squamous Cell Carcinoma of Head and Neck , Calreticulin , CD8-Positive T-Lymphocytes , Mice, Inbred C3H , Immunity , Tumor Microenvironment
19.
Bioact Mater ; 19: 237-250, 2023 Jan.
Article in English | MEDLINE | ID: mdl-35510176

ABSTRACT

The limited clinical response and serious side effect have been challenging in cancer immunotherapy resulting from immunosuppressive tumor microenvironment (TME) and inferior drug targeting. Herein, an active targeting TME nanoplatform capable of revising the immunosuppressive TME microenvironment is designed. Briefly, gold nanorods (GNRs) are covered with silica dioxide (SiO2) and then coated manganese dioxide (MnO2) to obtain GNRs@SiO2@MnO2 (GSM). Myeloid-derived suppressor cells (MDSCs) membrane is further camouflaged on the surface of GSM to obtain GNRs@SiO2@MnO2@MDSCs (GSMM). In this system, GSMM inherits active targeting TME capacity of MDSCs. The localized surface plasmon resonance of GNRs is developed in near-infrared II window by MnO2 layer coating, realizing NIR-II window photothermal imaging and photoacoustic imaging of GSMM. Based on the release of Mn2+ in acidic TME, GSMM can be also used for magnetic resonance imaging. In cancer cells, Mn2+ catalyzes H2O2 into ·OH for (chemodynamic therapy) CDT leading to activate cGAS-STING, but also directly acts on STING inducing secretion of type I interferons, pro-inflammatory cytokines and chemokines. Additionally, photothermal therapy and CDT-mediated immunogenic cell death of tumor cells can further enhance anti-tumor immunity via exposure of CRT, HMGB1 and ATP. In summary, our nanoplatform realizes multimodal cancer imaging and dual immunotherapy.

20.
J Colloid Interface Sci ; 629(Pt A): 971-980, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36152621

ABSTRACT

Oxygen reduction reaction (ORR) electrocatalysts with excellent activity and high selectivity toward the efficient four-electron (4e) pathway are very important for the wide application of fuel cells and are worth searching vigorously. In this study, r-RhTe monolayer is identified as a good ORR electrocatalyst from three 2D RhTe configurations with low Rh-loading (i.e., r-RhTe, o-RhTe and h-RhTe) on the basis of the first-principles calculations. For the most energetically stable r-RhTe, two adjacent positively charged Te atoms on the material surface can provide an active site for oxygen dissociation. Coupled with its high stability and intrinsic conductivity, 2D r-RhTe monolayer is confirmed to possess good catalytic activity and high reaction selectivity toward ORR. Moreover, under the ligand effect caused by the substitution of Cr, Mn and Fe, the ORR catalytic activity of r-RhTe monolayer could be effectively enhanced, where very small over-potential was achieved, and even comparable to or lower than the state-of-the-art Pt (111). This shows it has considerably high ORR activity. This work is highly anticipated to provide excellent candidate materials for ORR catalysis, and the related researches based on the Rh-Te materials will provide a new way to design high-performance ORR electrocatalysts to substitute the precious metal Pt-based catalysts.

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