Boosting Energy Deprivation by Synchronous Interventions of Glycolysis and Oxidative Phosphorylation for Bioenergetic Therapy Synergetic with Chemodynamic/Photothermal Therapy.

Bioenergetic therapy is emerging as a promising therapeutic approach. However, its therapeutic effectiveness is restricted by metabolic plasticity, as tumor cells switch metabolic phenotypes between glycolysis and oxidative phosphorylation (OXPHOS) to compensate for energy. Herein, Metformin (MET) and BAY-876 (BAY) co-loaded CuFe2O4 (CF) nanoplatform (CFMB) is developed to boost energy deprivation by synchronous interventions of glycolysis and OXPHOS for bioenergetic therapy synergetic with chemodynamic/photothermal therapy (CDT/PTT). The MET can simultaneously restrain glycolysis and OXPHOS by inhibiting hexokinase 2 (HK2) activity and damaging mitochondrial function to deprive energy, respectively. Besides, BAY blocks glucose uptake by inhibiting glucose transporter 1 (GLUT1) expression, further potentiating the glycolysis repression and thus achieving much more depletion of tumorigenic energy sources. Interestingly, the upregulated antioxidant glutathione (GSH) in cancer cells triggers CFMB degradation to release Cu+/Fe2+ catalyzing tumor-overexpressed H2O2 to hydroxyl radical (∙OH), both impairing OXPHOS and achieving GSH-depletion amplified CDT. Furthermore, upon near-infrared (NIR) light irradiation, CFMB has a photothermal conversion capacity to kill cancer cells for PTT and improve ∙OH production for enhanced CDT. In vivo experiments have manifested that CFMB remarkably suppressed tumor growth in mice without systemic toxicity. This study provides a new therapeutic modality paradigm to boost bioenergetic-related therapies.

Trichosanthin-derived peptide Tk-PQ attenuates immune rejection in mouse tracheal allotransplant model by suppressing PI3K-Akt and inducing type II immune polarization.

Obliterative bronchiolitis (OB) is one of the main complications affecting long-term survival of post-lung transplantation patients. In this study, we evaluated the efficacy of Tk-PQ (a peptide derived from trichosanthin) in alleviating OB in a mouse ectopic tracheal transplant model. We found that post-transplantation treatment of Tk-PQ significant ameliorated OB symptoms including luminal occlusion, epithelial cells loss and fibrosis in the allograft. In addition, Tk-PQ promoted immune suppressive environment by inducing Th2 polarization and increasing Treg population which in turn led to elevated levels of anti-inflammatory cytokines IL-4, IL-10, IL-33 and decreased levels of pro-inflammatory IL-1ß. Mechanistically, we used transcriptome analysis of splenic T cells from allografted mice to show that Tk-PQ treatment down-regulated the PI3K-Akt signaling pathway. Indeed, the immune suppression phenotypes of Tk-PQ was recapitulated by a PI3K inhibitor LY294002. Taken together, Tk-PQ regulates post-transplantation immuno-rejection by modulating the balance of T cell response via the PI3K-Akt pathway, making it a promising peptide based immune rejection suppressant for patients receiving allotransplant.

Effects of PKCε knockdown on mitochondrial membrane potential of human glioma cells in vitro and growth of U251 cell-derived tumors in vivo.

Glioma is the most common type of primary brain tumor; it exhibits great invasive capacity, morbidity and mortality. Protein kinase Cε (PKCε), a serine/threonine kinase, contributes to the development and progression of many cancers. We investigated whether knockdown of PKCε could affect the mitochondrial membrane potential of human glioma cell lines, U251 and U87, and the growth of U251 cell-derived tumors in nude mice. We found that the expression of PKCε was greater in human glioma tissues than in human normal brain tissues. Knockdown of PKCε reduced mitochondrial membrane potential in U251 and U87 cells. Knockdown of PKCε also suppressed the growth of tumors derived from U251 cells and induced apoptosis of U251 cells in vivo. Our findings indicate that PKCε is important for development and progression of glioma and may be a potential therapeutic target for glioma treatment.

Energy transfer mediated rapid and visual discrimination of tetracyclines and quercetin in food by using N, Cu Co-doped carbon dots.

The appearance of multi-drug resistant Escherichia coli makes the combination of tetracyclines (TCs) and quercetin (QCT) more common to fight stubborn bacterial infections so that the effective detections of TCs and QCT are essential and necessary. Here, a novel fluorescence probe for differentiating TCs and QCT is developed based on the nitrogen and copper co-doped carbon dots (N, Cu-CDs). The N, Cu-CDs are prepared from ethylene diamine tetraacetic acid (EDTA) and anhydrous copper chloride as precursors through hydrothermal process and exhibit bright blue fluorescence with excellent optical stability. With the presence of four tetracyclines (DOX, TC, CTC and OTC), the fluorescence intensity of N, Cu-CDs is quenched directly due to the internal filtration effect (IFE), and the detection limit obtained through single-signal fluorescence sensing is as low as 23.8 nM for DOX, 37.2 nM for TC, 43.8 nM for OTC and 28.8 nM for CTC. More remarkably, three dimensional ratiometric fluorescence probe for detecting QCT is proposed based on the appearance of another emission at (410 nm, 490 nm) due to electron transform (ET) process. This new method shows a good linear relationship in the range of 10-100 µM with a low detection limit of 59.3 nM. Furthermore, a dual-channel fluorescence sensing platform based on microfluidics paper-based analytical devices (µPADs) is developed for simultaneously visual discrimination of TCs (DOX is chosen as the typical detecting model for TCs) and QCT. This investigation provides a new way for the development of CDs as multifunction fluorescence probes.

Hydrogen peroxide self-sufficient and glutathione-depleted nanoplatform for boosting chemodynamic therapy synergetic phototherapy.

Chemodynamic therapy (CDT), which suppresses tumors via the conversion of endogenous hydrogen peroxide (H2O2) to highly toxic hydroxyl radicals (•OH), is deemed as a cutting-edge antitumor strategy. However, the insufficient endogenous H2O2 and up-regulated antioxidant glutathione (GSH) in the tumor microenvironment (TME) greatly impede the therapeutic effect of CDT. Herein, a versatile nanoplatform MgO2@SnFe2O4@PEG (MSnFeP) is elaborately fabricated for boosting CDT synergetic phototherapy. In the TME, the activation of MSnFeP contributes to in situ supply of H2O2, generation of •OH and consumption of GSH for boosted CDT. Furthermore, photothermal therapy (PTT) and photodynamic therapy (PDT) are simultaneously stimulated by near-infrared (NIR) light exposure on MSnFeP to increase the toxic free radical yield. This strategy not only amplifies the CDT efficacy hindered by H2O2 deficiency and GSH overexpression, but also further enhances the therapeutic effect with the combination of phototherapy.

H2O2 self-sufficient nanoplatform based on CeO2 QDs decorated MgO2 nanosheet for amplified chemodynamic therapy.

Chemodynamic therapy (CDT), which employs Fenton/Fenton-like agents to decompose hydrogen peroxide (H2O2) into toxic hydroxyl radical (•OH) to induce cancer cell apoptosis and necrosis, holds great promise in tumor therapy due to its high selectivity. Nevertheless, its efficiency is impaired by the insufficient intracellular H2O2 concentration and/or the insensitive response of Fenton/Fenton-like agents to the slightly acid tumor microenvironment (pH∼7.0-6.5). Herein, we develop a novel CDT reagent based on CeO2 quantum dot (QD) decorated MgO2 nanosheets engineered with cascade reactions to boost the intracellular H2O2 level and high pH-activated (pH = 6.5) characteristic for an enhanced CDT. Under the tumor microenvironment (pH = 6.5), MgO2 nanosheets that are highly reactive can react with H2O to produce nontoxic Mg2+ and abundant H2O2, boosting the intracellular H2O2 level. The self-generated H2O2 is subsequently converted into •OH by CeO2 QD, which is served as a relatively high pH-activated (pH = 6.5) Fenton-like agent. The sufficient intracellular H2O2 supply and sensitive response to the slightly acid tumor sites significantly improve the Fenton reaction, leading to the excellent in vivo CDT results with tumor growth inhibition effect. Our work presents a distinctive paradigm for self-boosting CDT efficacy.

OsFTL4, an FT-like Gene, Regulates Flowering Time and Drought Tolerance in Rice (Oryza sativa L.).

The initiation of flowering in cereals is a critical process influenced by environmental and endogenous signals. Flowering Locus T-like (FT-like) genes encode the main signals for flowering. Of the 13 FT-like genes in the rice genome, Hd3a/OsFTL2 and RFT1/OsFTL3 have been extensively studied and revealed to be critical for flowering. In this study, a rice FT-like gene, OsFTL4, was functionally characterized. Specifically, osftl4 mutants were generated using a CRISPR/Cas9 system. Compared with the wild-type control (Guangluai 4), the osftl4-1 and osftl4-2 mutants flowered 9.6 and 5.8 days earlier under natural long-day and short-day conditions, respectively. Additionally, OsFTL4 was mainly expressed in the vascular tissue, with the resulting OsFTL4 protein localized in both the nucleus and cytoplasm. Furthermore, OsFTL4 was observed to compete with Hd3a for the interaction with multiple 14-3-3 proteins. An analysis of the effects of simulated drought stress suggested that silencing OsFTL4 enhances drought tolerance by decreasing stomatal conductance and water loss. These results indicate that OsFTL4 helps integrate the flowering process and the drought response in rice.

Selective Detection of Nucleotides in Infant Formula Using an N-Rich Covalent Triazine Porous Polymer.

The aromatic structure and the rich nitrogen content of polymers based on covalent triazine-based frameworks (CTF) and their unique hydrophilic-lipophilic-balanced adsorption properties make them promising candidates for an adsorbent that can be used for sample pretreatment. Herein, a new covalent triazine-based framework (CTF-DBF) synthesized by a Friedel−Crafts reaction was used for the determination of the content of nucleotides in commercial infant formula. It was shown that the synthetic materials had an amorphous microporous structure, a BET surface area of up to 595.59 m2/g, and 0.39 nm and 0.54 nm micropores. The versatile adsorption properties of this material were evaluated by quantum chemistry theory calculations and batch adsorption experiments using five nucleotides as probes. The quantum chemistry results demonstrated that CTF-DBF can participate in multiple interactions with nucleotides. All the analyses performed present good linearity with R2 > 0.9993. The detection limits of targets ranged from 0.3 to 0.5 mg/kg, the spiked recoveries were between 85.8 and 105.3% and the relative standard deviations (RSD, n = 6) were between 1.1 and 4.5%. All these results suggest that this versatile CTF-DBF has great potential for sample pretreatment.

Novel EGFRvIII-CAR transgenic mice for rigorous preclinical studies in syngeneic mice.

BACKGROUND: Rigorous preclinical studies of chimeric antigen receptor (CAR) immunotherapy will require large quantities of consistent and high-quality CAR-transduced T (CART) cells that can be used in syngeneic mouse glioblastoma (GBM) models. To this end, we developed a novel transgenic (Tg) mouse strain with a fully murinized CAR targeting epidermal growth factor receptor variant III (EGFRvIII). METHODS: We first established the murinized version of EGFRvIII-CAR and validated its function using a retroviral vector (RV) in C57BL/6J mice bearing syngeneic SB28 GBM expressing EGFRvIII. Next, we created C57BL/6J-background Tg mice carrying the anti-EGFRvIII-CAR downstream of a Lox-Stop-Lox cassette in the Rosa26 locus. We bred these mice with CD4-Cre Tg mice to allow CAR expression on T cells and evaluated the function of the CART cells both in vitro and in vivo. To inhibit immunosuppressive myeloid cells within SB28 GBM, we also evaluated a combination approach of CART and an anti-EP4 compound (ONO-AE3-208). RESULTS: Both RV- and Tg-CART cells demonstrated specific cytotoxic activities against SB28-EGFRvIII cells. A single intravenous infusion of EGFRvIII-CART cells prolonged the survival of glioma-bearing mice when preceded by a lymphodepletion regimen with recurrent tumors displaying profound EGFRvIII loss. The addition of ONO-AE3-208 resulted in long-term survival in a fraction of CART-treated mice and those survivors demonstrated delayed growth of subcutaneously re-challenged both EGFRvIII+ and parental EGFRvIII- SB28. CONCLUSION: Our new syngeneic CAR Tg mouse model can serve as a useful tool to address clinically relevant questions and develop future immunotherapeutic strategies.

CeO2 QDs anchored on MnO2 nanoflowers with multiple synergistic effects for amplified tumour therapy.

Chemodynamic therapy (CDT) is an emerging tumour-specific therapeutic technology. However, the relatively insufficient catalytic activity of CDT agents in the tumour microenvironment (TME) limits their biomedical application. In addition, severe hypoxia and glutathione (GSH) overexpression in the TME greatly limit the antitumour efficiency of monotherapy. Herein, a cancer cell membrane-camouflaged and ultrasmall CeO2-decorated MnO2 (mMC) composite is developed for amplified CDT, photodynamic therapy (PDT) and photothermal therapy (PTT). Due to the homotypic targeting ability of cancer cell membranes, mMC nanoparticles preferentially accumulate in tumour tissue. In the TME, CeO2 acts as a highly efficient CDT agent to convert endogenous H2O2 to toxic reactive oxygen species (ROS) for killing cancer cells. Meanwhile, MnO2 irradiated with near-infrared (NIR) light displays prominent hyperthermia and ROS generation performance to perform PTT and PDT. Moreover, MnO2 can produce oxygen to ameliorate hypoxia and deplete GSH to relieve the antioxidant capability of tumours, which is beneficial to the simultaneous augmentation of PDT and CDT. Most importantly, the catalytic activity of CeO2 was greatly improved by hyperthermia. Consequently, a significantly enhanced therapeutic efficiency was obtained by the above multiple synergistic effects. This work provides a proof of concept for amplified tumour therapy by synchronously self-supplying oxygen, consuming GSH, and enhancing catalytic activity.

ELMO1 Regulates RANKL-Stimulated Differentiation and Bone Resorption of Osteoclasts.

Bone homeostasis is a metabolic balance between the new bone formation by osteoblasts and old bone resorption by osteoclasts. Excessive osteoclastic bone resorption results in low bone mass, which is the major cause of bone diseases such as rheumatoid arthritis. Small GTPases Rac1 is a key regulator of osteoclast differentiation, but its exact mechanism is not fully understood. ELMO and DOCK proteins form complexes that function as guanine nucleotide exchange factors for Rac activation. Here, we report that ELMO1 plays an important role in differentiation and bone resorption of osteoclasts. Osteoclast precursors derived from bone marrow monocytes (BMMs) of Elmo1-/- mice display defective adhesion and migration during differentiation. The cells also have a reduced activation of Rac1, p38, JNK, and AKT in response to RANKL stimulation. Importantly, we show that bone erosion is alleviated in Elmo1-/- mice in a rheumatoid arthritis mouse model. Taken together, our results suggest that ELMO1, as a regulator of Rac1, regulates osteoclast differentiation and bone resorption both in vitro and in vivo.

Bowl-like mesoporous polydopamine with size exclusion for highly selective recognition of endogenous glycopeptides.

It has been confirmed that endogenous glycopeptide plays an important role in a variety of pathological and physiological processes. However, direct analysis of endogenous glycopeptide is still a great challenge owing to the low abundance of endogenous glycopeptides and the presence of a large number of interfering substances such as large-sized proteins and heteropeptides in complex biological sample. Herein, we reported a novel bowl-like mesoporous polydopamine nanoparticle modified by carrageenan (denoted as MPDA@PEI@CA) with strong hydrophilicity and size-exclusion effect for high specificity enrichment of endogenous glycopeptides. Thanks to the suitable pore channel structure as well as strong hydrophilic surface, the as-prepared MPDA@PEI@CA nanoparticles exhibited prominent performance in enrichment of N-linked glycopeptide with ultrahigh selectivity (1:5000 M ratio of horseradish peroxidase (HRP) digests/bovine serum albumin (BSA) digests), low detection limit (5 fmol µL-1), outstanding size-exclusion ability (1:1000 mass of HRP/BSA), and unique reusability (five times). 125 N-glycosylation sites of 134 glycopeptides from 65 glycoproteins were identified from 2 µL sample of human serum treated with the MPDA@PEI@CA nanoparticles, which manifested the ability to enrich endogenous N-linked glycopeptides from complex biological samples. These results indicated that the bowl-like MPDA@PEI@CA nanoparticles with novel structure prepared in this work had great potential for glycopeptidome analysis.

Covalent Triazine Framework Sorbent for Solid Phase Extraction of Fipronil and its Metabolite in Eggs with Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry.

A solid-phase extraction (SPE) method was established for fipronil and its metabolite residues (fipronil desulfinyl, fipronil sulphone and fipronil sulphide) in eggs with a covalent triazine framework (CTF) porous material as the adsorbent followed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) detection. Multiple probes and quantum chemistry theory calculations were conducted to describe the versatile adsorption property directly and quantifiably. The conjugated structure of CTF and N-containing triazine generated π-π interactions and hydrogen bonds between the CTF and the targets, which led to high extraction efficiency and recoveries. The solid-phase extraction parameters, including amount of the adsorbent, type of eluent, amount of eluent and loading rate were investigated. Under the optimal experimental conditions, the recoveries of the analytes were between 85.5% and 103.2%, and the RSD (n = 5) was between 1.8% and 3.6%. The LODs and LOQs were 0.13-0.2 ng g-1 and 0.5-0.8 ng g-1, respectively. The sorbent can effectively reduce the interference of the matrix and meet the detection requirements of fipronil and its metabolites in eggs. These results imply that the CTF as adsorbents have great potential in the analysis of trace targets in samples with complex matrices.

Biodegradable flower-like manganese for synergistic photothermal and photodynamic therapy applications.

A flower-like nanostructured MnO2 with near-infrared (NIR) light-triggered high photothermal conversion capability of 30% and reactive oxygen species (ROS) generation ability was successfully developed. Different from the reported MnO2 nanomaterials those were used in the nanomedicine field for only relieving tumor hypoxia and/or imaging, the flower-like MnO2 inherently acts as a competent agent for simultaneously enhanced photothermal and photodynamic therapy. A flower-like nanostructured MnO2 with near-infrared (NIR) light triggered high photothermal conversion capability of 30% and reactive oxygen species (ROS) generation ability was successfully developed.

[Progress in functions and mechanisms of immunosuppressive neutrophil subsets: An update].

Neutrophils are the most abundant circulating leukocytes in healthy adults, serving as the first-line defense against infections. In the last few years, scientists have reported neutrophils of immune suppressive properties, such as tumor-associated neutrophils (TAN) and low-density neutrophils (LDN). These neutrophils are found to be involved in many physiological and pathological conditions owing to their ability of regulating T cell functions and promoting angiogenesis and tumor growth through a number of mechanisms, including PD-1/PD-L1, antigen presentation, reactive oxygen species (ROS), arginase-1 (Arg1), inducible nitric oxide synthase (iNOS), etc. This review summarizes the recent advances in investigating the function and mechanism of immune suppressive neutrophils.

Ultra-high sensitivity of multicolor Sm3+-doped LiSrVO4 phosphors for contactless optical thermometers.

To overcome the existing challenge of temperature monitoring with high accuracy, we designed Sm3+-doped LiSrVO4 phosphors with ultra-high sensitivity as promising candidates for optical thermometers. The prepared samples could emit multicolor emissions after excitation at 343 nm and the optimum doping concentration for the Sm3+ ions in the selected host was 1 mol%. The mechanism of energy transfer from the VO43- group to the Sm3+ ions was studied and its efficiency was proved to be 84.1% for an Sm3+ ion content of 7 mol%. Based on the disparate thermal quenching performances of the VO43- group and Sm3+ ions, the temperature monitoring ability of the prepared compounds was examined. Through choosing different emissions of Sm3+ ions, and then combining them with the VO43- group, optical thermometers with controllable sensitivity were realized. The maximum absolute and relative sensitivities of the resultant phosphors could reach ultra-high values of 1.076 K-1 and 6.167% K-1, respectively, which were the highest sensitivities reported so far. Furthermore, the doping content also impacted the sensitivities of the resultant compounds.

LncRNA ST8SIA6-AS1 promotes proliferation, migration and invasion in breast cancer through the p38 MAPK signalling pathway.

Long non-coding RNAs (lncRNAs) are regarded as important functional regulators of various biological processes and are also known to be involved in the occurrence and development of human cancers, including breast cancer (BC). In our present study, the RNA expression profiling data for a large cohort of human BC samples were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the differentially expressed lncRNAs were screened out. We found that the expression of ST8SIA6-AS1 was elevated in BC tumour tissues compared with the adjacent normal tissues in the samples from the TCGA and GEO datasets, as well as in 138 BC tissue samples obtained by us. The high expression of ST8SIA6-AS1 was associated with estrogen receptor-negative, progesterone receptor-negative, advanced tumour-node-metastasis stage and worse survival in BC patients. In vitro functional studies revealed that high expression of ST8SIA6-AS1 promoted proliferation, invasion and migration of BC cell lines. The results of the in vivo studies indicated that upregulation of ST8SIA6-AS1 promoted xenograft tumour growth of BC. Mechanistically, ST8SIA6-AS1 regulated AKT1 and p38 mitogen-activated protein kinase (MAPK) gene expression by affecting their mRNA and protein levels, respectively, and it also affected the phosphorylation of AKT1 protein. Rescue experiments indicated that ST8SIA6-AS1 promoted BC cell proliferation, invasion and migration in a p38 MAPK signalling-mediated manner. Together, our data suggest that ST8SIA6-AS1 plays an important role in the occurrence and development of BC and may therefore serve as a promising therapeutic target.

Ultralow-intensity near infrared light synchronously activated collaborative chemo/photothermal/photodynamic therapy.

Although combined chemotherapy (Chemo), photothermal (PTT) and photodynamic (PDT) in cancer therapy has drawn significant attention due to its superior anticancer ability, the required high intensity of irradiation results in serious photo-toxicity to healthy neighboring cells, and thus limits its biomedical applications. Herein, we developed an ultralow-intensity near infrared (NIR) light synchronously activated collaborative Chemo/PTT/PDT nanoplatform. The nanoplatform is composed of a highly emissive upconversion (UC) core, chlorin e6 (Ce6) photosensitizer and the anticancer drug doxorubicin hydrochloride (DOX) co-loaded in a mesoporous silica (MS) shell, and polyethylene glycol-modified graphene (PGO) acts as both the photothermal reagent and smart switch for promoted drug release. Upon 808 nm NIR light exposure with ultralow intensity (0.25 W cm-2), which is below the maximum permissible exposure (MPE, 0.33 W cm-2) for skin, the mild hyperpyrexia of PGO induced both cancer cell irreversible death for PTT and greatly promoted drug release for enhanced Chemo. On the other hand, the upconverted 660 nm light from UC activated Ce6 to generate reactive oxygen species for PDT, while the upconverted 540 nm light from UC could be employed for visualizing the treatment process. The in vitro and in vivo anticancer experiments demonstrate that the ultralow-intensity NIR light synchronously activated Chemo/PTT/PDT nanoplatform exhibits remarkable therapeutic efficacy with minimal photodamage.

Ratiometric optical thermometer based on the use of manganese(II)-doped Cs3Cu2I5 thermochromic and fluorescent halides.

The inconsistent thermal quenching performance of manganese(II)-doped Cs3Cu2I5 microparticles is exploited in a highly sensitive noninvasive optical thermometer. The ratio of the emissions of Cu(II) and Mn(II) ions in the microparticles is highly temperature dependent in the range from 298 to 498 K. The best absolute and relative sensitivities are 0.547 K-1 and 0.525% K-1, respectively. The emission spectrum, under 300-nm photoexcitation, has emission peaks at 448 and 556 nm. This is the result of energy transfer between the Cu(II) and Mn(II) ions whose efficiency can reach up to 57% when the Mn(II) ion concentration is 2 mol%. The emission color of the microparticles changes from cyan to green when increasing the temperature from 298 to 498 K. Graphical abstract Synthesis of novel Mn(II)-doped Cs3Cu2I5 thermochromic halides with admirable luminescent behaviors for high sensitive ratiometric thermometry and safety sign in high temperature environment.

BaTiO3/MWNTs/Polyvinylidene Fluoride Ternary Dielectric Composites with Excellent Dielectric Property, High Breakdown Strength, and High-Energy Storage Density.

To improve the dielectric performance of polyvinylidene fluoride (PVDF), BaTiO3/MWNTs/PVDF ternary composites were prepared by the solution casting method. The percolation threshold (fraction of MWNTs) has dropped greatly below 0.4 vol %, with the enhancement of dielectric constant and breakdown field. For the BaTiO3/MWNTs/PVDF (11.5/0.35/88.15) composite, the dielectric constant is 59, the loss is below 0.055, and the maximum operating electric field is 324 MV/m, so the discharged energy density can be of up to 10.3 J/cm3 with the efficiency of above 77.2%. The reason of improvement was revealed by the scanning electron microscope images and the X-ray diffraction data. It is found that uniform distribution of filler in the composites and the increase of the ß phase of polymers result in the enhancement of polarization and improvement of dielectric constant of PVDF. The third-phase spherical inorganic particles prevent the formation of conductive networks and improve the uniformity of local electric field, so the breakdown strength of composites can be enhanced greatly. Here, this paper provides a method to get the composites with high energy storage density for supercapacitors.