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1.
The combination of chemo‐ and immunotherapy represents one promising strategy to overcome the existent challenges in the present‐day anticancer therapy. Here, spermine‐modified acetalated dextran nanoparticles (Sp‐AcDEX NPs), co‐loaded with the non‐genotoxic molecule Nutlin‐3a (Nut3a), and the cytokine granulocyte–macrophage colony‐stimulating factor (GM‐CSF), are developed to induce cancer cell death and create a specific antitumor immune response. These polymeric NPs release Nut3a in a pH dependent fashion and induce endosomal escape. Due to Nut3a, the loaded NPs exert specific toxicity toward wild‐type p53 cancer cells while avoiding toxicity in immune cells. Furthermore, the NPs show intrinsic immune adjuvancy on monocyte derived‐dendritic cells, upregulating the expression of cell surface CD83 and CD86 costimulatory markers. Finally, it is examined that by inducing MCF‐7 breast cancer cell death and acting as immune adjuvants, the NPs can downregulate the expression of IL‐10 and upregulate IL‐1β, leading to proliferation of CD3+ and cytotoxic CD8+ T cells. Overall, the study suggests that Sp‐AcDEX NPs loaded with Nut3a and GM‐CSF is a promising system for chemo‐immunotherapy, capable of inducing tumor cell death and stimulating immune response.  相似文献   

2.
Tumor metastasis and relapse mainly results in therapy failure and becomes a big challenge in oncology. Immunogenic cell death (ICD) of tumors mediated immunotherapy (IT) is attracting widely for solving that problem although achieving sufficient ICD and strong immune response is challenging for nanoparticles-based cancer IT. Herein, a multifunctional polypeptide coordinate nanocomposite that possesses near infrared photothermia (PT) and responsive releases of nitric oxide (NO) and iron ions is constructed, which synergistically kills cancer cells and highly prohibits metastatic 4T1 cells invasion and migration by PT-boosted NO release and ferroptosis (FT). Remarkably, triple FT-NO-PT treatment amplifies the ICD effects and outperforms combo/monotherapy FT-PT and FT in cancer cells and tumors, which further activates dendritic cells maturation, and primed CD4+T and CD8+T cells immune responses and memory effects, playing four birds with one stone (i.e., FT-NO-PT-IT). The PCSFG-based FT-NO-PT not only fully eradicates 4T1 primary tumors, but also induces strong ICD, immune priming, and memory effects to reject rechallenged 4T1 tumors and inhibit malignant tumor metastasis, demonstrating synergistic amplified ICD effects with strong cell immunities and memory effects by a unified FT-NO-PT-IT.  相似文献   

3.
Subunit vaccines use delivery platforms to present minimal antigenic components for immunization. The benefits of such systems include multivalency, self‐adjuvanting properties, and more specific immune responses. Previously, the design, synthesis, and characterization of self‐assembling peptide cages (SAGEs) have been reported. In these, de novo peptides are combined to make hubs that assemble into nanoparticles when mixed in aqueous solution. Here it is shown that SAGEs are nontoxic particles with potential as accessible synthetic peptide scaffolds for the delivery of immunogenic components. To this end, SAGEs functionalized with the model antigenic peptides tetanus toxoid632‐651 and ovalbumin323‐339 drive antigen‐specific responses both in vitro and in vivo, eliciting both CD4+ T cell and B cell responses. Additionally, SAGEs functionalized with the antigenic peptide hemagglutinin518‐526 from the influenza virus are also able to drive a CD8+ T cell response in vivo. This work demonstrates the potential of SAGEs to act as a modular scaffold for antigen delivery, capable of inducing and boosting specific and tailored immune responses.  相似文献   

4.
Most vaccines are designed to attack tumor cells by activating CD4+/CD8+ αβ T cells. Unfortunately, αβ T cells, which only recognize the peptide antigens in the complexes with polymorphic MHCI/II molecules, surrender to the tumor heterogenicity. As another subset of T cells, γδ T cells become salient in antitumor because of their unique immunotherapeutic roles. Herein, a tumor vaccine is developed with multivalent antigens by fusion of tumor cell membranes with lipids and successfully activated γδ T cells via microneedle inoculation. It is certified that the evoked γδ T cells synchronize with αβ T cells revitalizing tumor-induced immunotolerance. In turn, the tumors of mice are significantly inhibited and their median survival time is prolonged considerably. Moreover, the nanovaccine inhibits tumor recurrence after resection. The therapeutic effects are corroborated with the results from TCRδ−/− mice as well as cytokine expression in tumor.  相似文献   

5.
Natural polymer nanofibers are attractive sustainable raw materials to fabricate separators for high‐performance lithium ion batteries (LIBs). Unfortunately, complicated pore‐forming processes, low ionic conductivity, and relatively low mechanical strength of previously reported natural polymer nanofiber‐based separators severely limit their performances and applications. Here, a chemical modification strategy to endow high performance to natural polymer nanofiber‐based separators is demonstrated by grafting cyanoethyl groups on the surface of chitin nanofibers. The fabricated cyanoethyl‐chitin nanofiber (CCN) separators not only exhibit much higher ionic conductivity but also retain excellent mechanical strength in comparison to unmodified chitin nanofiber separators. Through density function theory calculations, the mechanism of high Li+ ion transport in the CCN separator is unraveled as weakening of the binding of Li+ ions over that of PF6? ions with chitin, via the cyanoethyl modification. The LiFePO4/Li4Ti5O12 full cells using CCN separators show much better rate capability and enhanced capacity retention compared to the cell using commercial polypropylene (PP) separators. Beyond this, the CCN separator can work very well even at an elevated temperature of 120 °C in the LiFePO4/Li cell. The proposed strategy chemical modification of natural polymer nanofibers will open a new avenue to fabricate sustainable separators for LIBs with superior performance.  相似文献   

6.
The combination of BRAF/MEK‐targeted therapy with immune checkpoint blockade is regarded as a promising regimen for patients with metastatic melanoma due to their complementary advantages. However, MEK‐inhibitor‐induced T‐cell toxicity impedes effective cooperation. In this experiment, a pH‐responsive on‐demand controlled release mesoporous silica nanoparticles (MSNPs) system is designed. Fluorescein‐isothiocyanate‐loaded MSNP can be specifically delivered into tumor cells rather than T‐cells. MEK‐inhibitor‐loaded MSNP avoids proliferative and functional inhibitions of T‐cells, while preserving growth suppression of tumor cells in vitro. In an in vivo model, MSNP encapsulation reverses the MEK‐inhibitor‐induced suppression of activated CD8+ T‐cells, and enhances the secretion of INF‐γ and IL‐2. The combination of BRAF inhibitor plus MSNP‐loaded MEK inhibitor and anti‐PD‐1 antibody synergistically inhibits tumor growth via promoting robust immune‐related antitumor response. This work provides a novel and generalized framework for combining T‐cell‐impaired targeted therapy and immune checkpoint blockade by using a nanoparticle‐based delivery system.  相似文献   

7.
With the aim to design addressable magnetically‐active carbon nanotubes (CNTs) for cancer treatment, the use of Fe‐filled CNTs (Fe@MWCNTs) as multifunctional scaffolds is reported for exohedrally anchoring a monoclonal antibody (mAb) known to bind a plasma membrane receptor over‐expressed in several cancer cells (EGFR). Comprehensive microscopic (transmission electron microscopy, atomic force microscopy, and scanning electron microscopy) and spectroscopic (Raman, 57Fe Mossbauer, energy dispersive spectroscopy, X‐ray photoelectron spectroscopy (XPS), X‐ray diffraction) characterizations reveal the efficient confinement of magnetically‐active Fe phases (α‐Fe and Fe3C), while compositional evaluations through XPS, thermogravimetric analysis and gel electrophoresis confirm that mAb immobilization onto Fe@MWCNTs occurs. Enzyme‐linked immunosorbent assay (ELISA), confocal microscopy imaging and western blotting confirm the targeting action toward EGFR‐overexpressing cell lines (EGFR+). In vitro magnetic filtration experiments demonstrate that a selective removal of EGFR+ cells from a mixed population of healthy cell lines could be obtained in very short times (≈10 min). Cytotoxicity evaluations by classic cell staining procedures after application of an electromagnetic radiation inducing magnetic fluid hyperthermia (MFH), show a selective suppression of the EGFR+ cell line. Molecular dynamics and docking simulations of the hybrid mAb/Fe@MWCNTs conjugates nicely show how the presence of the CNT framework does not sterically affect the conformational properties of the two antigen binding regions, further supporting the biochemical findings.  相似文献   

8.
To face the increasing demand of self‐healing hydrogels with biocompatibility and high performances, a new class of cellulose‐based self‐healing hydrogels are constructed through dynamic covalent acylhydrazone linkages. The carboxyethyl cellulose‐graft‐dithiodipropionate dihydrazide and dibenzaldehyde‐terminated poly(ethylene glycol) are synthesized, and then the hydrogels are formed from their mixed solutions under 4‐amino‐DL‐phenylalanine (4a‐Phe) catalysis. The chemical structure, as well as microscopic morphologies, gelation times, mechanical and self‐healing performances of the hydrogels are investigated with 1H NMR, Fourier transform infrared spectroscopy, atomic force microscopy, rheological and compression measurements. Their gelation times can be controlled by varying the total polymer concentration or 4a‐Phe content. The resulted hydrogels exhibit excellent self‐healing ability with a high healing efficiency (≈96%) and good mechanical properties. Moreover, the hydrogels display pH/redox dual responsive sol‐gel transition behaviors, and are applied successfully to the controlled release of doxorubicin. Importantly, benefitting from the excellent biocompatibility and the reversibly cross‐linked networks, the hydrogels can function as suitable 3D culture scaffolds for L929 cells, leading to the encapsulated cells maintaining a high viability and proliferative capacity. Therefore, the cellulose‐based self‐healing hydrogels show potential applications in drug delivery and 3D cell culture for tissue engineering.  相似文献   

9.
The screen‐printing method is an economical metallization technique used by most manufacturers of conventional silicon solar cells. This method limits the cells' use under concentrated light owing to high series resistance losses caused, among other reasons, by low metal density in the fingers. This paper describes increasing the finger metal density by electrolytic deposition. The electrolytic deposition of silver is an economical, controllable and readily commercializable deposition method to reduce the front and back metallization series resistance contributions. With an optimized grid design, compatible with 1 sun silicon cell technology, and later electrolytic silver deposition we have obtained cells that maintain their efficiency up to 15 suns. In addition, an analysis of the performance of these cells under uniform and non‐uniform illumination were carried out on n+p and n+pn+ structures. Copyright © 2004 John Wiley & Sons, Ltd.  相似文献   

10.
Conventional oxygen‐dependent photodynamic therapy (PDT) has faced severe challenges because of the non‐specificity of most available photosensitizers (PSs) and the hypoxic nature of tumor tissues. Here, an O2 self‐sufficient cell‐like biomimetic nanoplatform (CAT‐PS‐ZIF@Mem) consisting of the cancer cell membrane (Mem) and a cytoskeleton‐like porous zeolitic imidazolate framework (ZIF‐8) with the embedded catalase (CAT) protein molecules and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4, defined as PS) is developed. Because of the immunological response and homologous targeting abilities of the cancer cell membrane, CAT‐PS‐ZIF@Mem is selectively accumulated at the tumor site and taken up effectively by tumor cells after intravenous injection. After the intracellular H2O2 penetration into the framework, it is catalyzed by CAT to produce O2 at the hypoxic tumor site, facilitating the generation of toxic 1O2 for highly effective PDT in vivo under near‐infrared irradiation. By integrating the immune escape, cell homologous recognition, and O2 self‐sufficiency, this cell‐like biomimetic nanoplatform demonstrates highly specific and efficient PDT against hypoxic tumor cells with much reduced side‐effect on normal tissues.  相似文献   

11.
Repair of bone defects with irregular shapes or at soft tissue insertion sites faces a huge challenge. Scaffolds capable of adapting to bone cavities, generating stiffness gradients, and inducing osteogenesis are necessary. Herein, a superelastic 3D ceramic fibrous scaffold is developed by assembly of intrinsically rigid, structurally flexible electrospun SiO2 nanofibers with chitosan as bonding sites (SiO2 NF‐CS) via a lyophilization technique. SiO2 NF‐CS scaffolds exhibit excellent elasticity (full recovery from 80% compression), fast recovery rate (>500 mm min?1), and good fatigue resistance (>10 000 cycles of compression) in an aqueous medium. SiO2 NF‐CS scaffolds induce human mesenchymal stem cell (hMSC) elongation and differentiation into osteoblasts. In vivo self‐fitting capability is demonstrated by implanting compressed SiO2 NF‐CS scaffolds into different shaped mandibular defects in rabbits, with a spontaneous recovery and full filling of defects. Rat calvarial defect repair validates enhanced bone formation and vascularization by cell (hMSC) histomorphology analysis. Further, subchondral bone scaffolds with gradations in SiO2 nanofibers are developed, leading to a stiffness gradient and spatially chondrogenic and osteogenic differentiation of hMSCs. This work presents a type of 3D ceramic fibrous scaffold, which can closely match bone defects with irregular shapes or at different implant sites, and is promising for clinical translation.  相似文献   

12.
Spectral response of solar cells determines the output performance of the devices. In this work, a 20.0% efficient silicon (Si) nano/microstructures (N/M‐Strus) based solar cell with a standard solar wafer size of 156 × 156 mm2 (pseudo‐square) has been successfully fabricated, by employing the simultaneous stack SiO2/SiNx passivation for the front N/M‐Strus based n+‐emitter and the rear surface. The key to success lies in the excellent broadband spectral responses combining the improved short‐wavelength response of the stack SiO2/SiNx passivated Si N/M‐Strus based n+‐emitter with the extraordinary long‐wavelength response of the stack SiO2/SiNx passivated rear reflector. Benefiting from the broadband spectral response, the highest open‐circuit voltage (Voc) and short‐circuit current density (Jsc) reach up to 0.653 V and 39.0 mA cm?2, respectively. This high‐performance screen‐printed Si N/M‐Strus based solar cell has shown a very promising way to the commercial mass production of the Si based high‐efficient solar cells.  相似文献   

13.
Immune checkpoint therapy (ICT) has the potential to treat cancer by removing the immunosuppressive brakes on T cell activity. However, ICT benefits only a subset of patients because most tumors are “cold”, with limited pre‐infiltration of effector T cells, poor immunogenicity, and low‐level expression of checkpoint regulators. It has been previously reported that Cowpea mosaic virus (CPMV) promotes the activation of multiple innate immune cells and the secretion of pro‐inflammatory cytokines to induce T cell cytotoxicity, suggesting that immunostimulatory CPMV could potentiate ICT. Here it is shown that in situ vaccination with CPMV increases the expression of checkpoint regulators on Foxp3?CD4+ effector T cells in the tumor microenvironment. It is shown that combined treatment with CPMV and selected checkpoint‐targeting antibodies, specifically anti‐PD‐1 antibodies, or agonistic OX40‐specific antibodies, reduced tumor burden, prolonged survival, and induced tumor antigen‐specific immunologic memory to prevent relapse in three immunocompetent syngeneic mouse tumor models. This study therefore reveals new design principles for plant virus nanoparticles as novel immunotherapeutic adjuvants to elicit robust immune responses against cancer.  相似文献   

14.
High and stable lifetimes recently reported for n‐type silicon materials are an important and promising prerequisite for innovative solar cells. To exploit the advantages of the excellent electrical properties of n‐type Si wafers for manufacturing simple and industrially feasible high‐efficiency solar cells, we focus on back junction n+np+ solar cells featuring an easy‐to‐fabricate full‐area screen‐printed aluminium‐alloyed rear p+ emitter. Independently confirmed record‐high efficiencies have been achieved on n‐type phosphorus‐doped Czochralski‐grown silicon material: 18·9% for laboratory‐type n+np+ solar cells (4 cm2) with shadow‐mask evaporated front contact grid and 17·0% for front and rear screen‐printed industrial‐type cells (100 cm2). The electrical cell parameters were found to be perfectly stable under illumination. Copyright © 2006 John Wiley & Sons, Ltd.  相似文献   

15.
The K+‐induced formation of G‐quadruplexes provides a versatile motif to lock or unlock substrates trapped in the pores of mesoporous SiO2 nanoparticles, MP‐SiO2 NPs. In one system, the substrate is locked in the MP‐SiO2 NPs by K+‐ion‐stabilized G‐quadruplex units, and the pores are unlocked by the elimination of K+ ions using Kryptofix [2.2.2] (KP) or 18‐crown‐6‐ether (CE) from the G‐quadruplexes. In the second system, the substrate is locked in the pores by means of K+‐stabilized aptameric G‐quadruplex/thrombin units. Unlocking of the pores is triggered by the dissociation of the aptamer/thrombin complexes through the KP‐ or CE‐mediated elimination of the stabilizing K+ ions. In the third system, duplex DNA units lock the pores of MP‐SiO2 NPs, and the release of the entrapped substrate is stimulated by the K+‐ion‐induced dissociation of the duplex caps through the formation of the K+‐stabilized G‐quadruplexes. The latter system is further implemented to release the anti‐cancer drug, doxorubicin, in the presence of K+ ions, from the MP‐SiO2 NPs. Preliminary intracellular experiments reveal that doxorubicin‐loaded MP‐SiO2 NPs lead to effective death of breast cancer cells.  相似文献   

16.
The disproportionation of polysulfide (PS) is a long‐neglected and vital issue that causes the fast capacity fading of Li–S batteries. Based on the hard and soft acids and bases (HSAB) theory, a large size N‐methyl‐N‐ethyl pyrrolidinium (MEP+) cation is proposed to complex and stabilize the PS in electrolyte. The disproportionation of PS is successfully suppressed by this simple method, thereby avoiding the precipitation of sulfur in the electrolyte and reducing the loss of the active materials. The mutual interaction mechanism between MEP+ and Sn2? in electrolyte is comprehensively investigated and verified for the first time, via both density functional theory (DFT) calculation and experimental characterization. It enables the 5000 mA h Li–S batteries (soft package type) to achieve initial specific energy over 300 Wh kg?1 and maintain over 65% after 100 charge/discharge cycles at 1/20 C, while merely 24% is remained at 59 cycles without MEP+. This interesting finding is believed to shed light on the further development of Li–S batteries.  相似文献   

17.
Carrier selective passivated contacts composed of thin oxide, n + polycrystalline Si and metal on top of a n‐Si absorber can significantly lower the recombination current density (Jorear ≤8 fA/cm2) under the contact while providing excellent specific contact resistance (5–10 mΩ‐cm2); 25.1% efficient small area cells with photolithography front contacts on boron doped selective emitter and Fz wafers have been achieved by Fraunhofer ISE using their tunnel oxide passivated contact (TOPCon) approach. This paper shows a methodology to model such passivated contact cells using Sentaurus device model, which involves replacing the TOPCon region by carrier selective electron and hole recombination velocities to match the measured Jorear of the TOPCon region as well as all the light IV values of the cell. We first validated the methodology by modeling a 24.9% reference cell. The model was then extended to assess the efficiency potential of large area TOPCon cells on commercial grade n‐type Cz material with screen‐printed front contacts. To use realistic input parameters, a 21% n‐type PERT cell was fabricated on Cz wafer (5 Ω‐cm, 1.5‐ms lifetime). Modeling showed that the cell efficiency will improve to only 21.6% if the back of this cell is replaced by the above TOPCon, and the performance is limited by the homogenous emitter. Efficiency was then modeled to improve to 22.6% with the implementation of selective emitter (150/20 Ω/sq). Finally, it is shown that screen printing of 40‐µm‐wide lines and improved bulk material (10 Ω‐cm, 3‐ms lifetime) can raise the single side TOPCon Cz cell efficiency to 23.2%. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   

18.
We recently introduced the buried emitter back‐junction solar cell, featuring large area fractions of overlap between n+‐type and p+‐type regions at the rear side of the device. In this paper we analyse the performance of the buried emitter solar cell (BESC) and its generalisations by one‐dimensional device simulations and analytical model calculations. A key finding is that the generalised versions of the BESC structure allows achieving very high efficiencies by passivating virtually the entire surface of p‐type emitters by an oxidised n‐type surface layer. A disadvantage of this type of full‐area emitter passivation in the generalised back‐junction BESC is the need for an insulating layer between the metallisation of the emitter and the contact to the base, which is technologically difficult to achieve. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   

19.
The difficulty in spinal cord regeneration is related to the inhibitory factors for axon growth and the lack of appropriate axon guidance in the lesion region. Here scaffolds are developed with aligned nanofibers for nerve guidance and drug delivery in the spinal cord. Blended polymers including poly(L ‐lactic acid) (PLLA) and poly(lactide‐co‐glycolide) (PLGA) are used to electrospin nanofibrous scaffolds with a two‐layer structure: aligned nanofibers in the inner layer and random nanofibers in the outer layer. Rolipram, a small molecule that can enhance cAMP (cyclic adenosine monophosphate) activity in neurons and suppress inflammatory responses, is immobilized onto nanofibers. To test the therapeutic effects of nanofibrous scaffolds, the nanofibrous scaffolds loaded with rolipram are used to bridge the hemisection lesion in 8‐week old athymic rats. The scaffolds with rolipram increase axon growth through the scaffolds and in the lesion, promote angiogenesis through the scaffold, and decrease the population of astrocytes and chondroitin sulfate proteoglycans in the lesion. Locomotor scale rating analysis shows that the scaffolds with rolipram significantly improved hindlimb function after 3 weeks. This study demonstrates that nanofibrous scaffolds offer a valuable platform for drug delivery for spinal cord regeneration.  相似文献   

20.
Up‐conversion (UC) luminescent and porous NaYF4:Yb3+, Er3+@SiO2 nanocomposite fibers are prepared by electrospinning process. The biocompatibility test on L929 fibrolast cells reveals low cytotoxicity of the fibers. The obtained fibers can be used as anti‐cancer drug delivery host carriers for investigation of the drug storage/release properties. Doxorubicin hydrochloride (DOX), a typical anticancer drug, is introduced into NaYF4:Yb3+, Er3+@SiO2 nanocomposite fibers (denoted as DOX‐NaYF4:Yb3+, Er3+@SiO2). The release properties of the drug carrier system are examined and the in vitro cytotoxicity and cell uptake behavior of these NaYF4:Yb3+, Er3+@SiO2 for HeLa cells are evaluated. The release of DOX from NaYF4:Yb3+, Er3+@SiO2 exhibits sustained, pH‐sensitive release patterns and the DOX‐NaYF4:Yb3+, Er3+@SiO2 show similar cytotoxicity as the free DOX on HeLa cells. Confocal microscopy observations show that the composites can be effectively taken up by HeLa cells. Furthermore, the fibers show near‐infrared UC luminescence and are successfully applied in bioimaging of HeLa cells. The results indicate the promise of using NaYF4:Yb3+, Er3+@SiO2 nanocomposite fibers as multi‐functional drug carriers for drug delivery and cell imaging.  相似文献   

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