Acta Biomaterialia
·
2025
·
IF 9.6
Nan Zhong,Ziyue Zu,Yishi Lu,Xuan Sha,Yang Li,Yang Liu,Shangyu Lu,Xi Luo,Yan Zhou,Jun Tao,Feiyun Wu,Zhaogang Teng,Yuxia Tang,Shouju Wang
Activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway could effectively initiate antitumor immunity in triple-negative breast cancer. However, current nuclear DNA-mediated activation of STING pathway remains constrained by the tight protection of nuclear membrane and histones, highlighting the need for new strategies to enhance its efficacy. Mitochondrial DNA (mtDNA), in contrast, is more vulnerable to damage. Herein, our nanoplatforms exploited the high glutathione (GSH) environment characteristic of tumors to release abundant Mn 2+ , which induced mitochondrial dysfunction and the release of endogenous mtDNA. The released mtDNA, in conjunction with Mn 2+ itself functioning as a strong cGAS agonist, effectively activated cGAS-STING pathway. Consequently, the cGAS-STING-dependent secretion of type I interferon successively enhanced the maturation of dendritic cells and cross-priming of CD8 + T cells. In a poorly immunogenic 4T1 tumor model, TPP-MMONs efficiently primed systemic antitumor immunity and significantly enhanced the therapeutic efficacy of αPD-L1 therapy, suppressing tumor growth in both localized and metastatic tumor models. These findings provided an innovative and straightforward strategy to enhance TNBC immunogenicity by targeting mitochondrial damage to induce mtDNA-mediated cGAS-STING activation, thereby sensitizing tumors to immune checkpoint inhibitor therapy. Statement of Significance The cGAS-STING pathway is a promising target for overcoming immunoresistance in TNBC. However, current nuclear DNA-based activation strategies are limited by the tight protection of nuclear membrane and histones. Herein, we reported novel manganese-rich, mitochondria-targeting nanoplatforms (TPP-MMONs), which can release abundant Mn²⁺ and significantly induce mitochondrial dysfunction, leading to the release of mtDNA. As a result, the nanoplatforms can effectively stimulate the cGAS-STING pathway, thereby enhancing immune responses and improving the therapeutic efficacy of αPD-L1 therapy, offering new insights into TNBC treatments.
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DOI
PubMed
高影响因子
Nanoscale
·
2021
·Vol. 13
·期 19
·8998-9008
·
IF 7.79
Xupeng Mu,Meng Zhang,Anhui Wei,Fei Yin,Yan Wang,Kebang Hu,Jinlan Jiang
Programmed cell death ligand 1 (PD-L1) blockade has achieved great success in cancer immunotherapy. PD-L1 siRNA can restore the immune anti-tumor activity of T cells by downregulating the level of PD-L1 on tumor cells, but the efficiency of PD-1/PD-L1 monotherapy is relatively low. Doxorubicin (DOX) can induce tumor cell apoptosis, and then increase the release of tumor antigen. But the expression of PD-L1 in tumor tissues treated with DOX will be enhanced adaptively. Therefore, DOX combination with PD-L1 siRNA can produce a good synergistic anti-tumor effect. In this study, stem cell membrane (SCM) camouflaged polydopamine nanoparticles carrying DOX and PD-L1 siRNA (PDA–DOX/siPD-L1@SCM) were constructed for targeting prostate cancer (PCa) bone metastases. PDA–DOX/siPD-L1@SCM NPs could effectively enhance blood retention and improve accumulation at tumor sites. In vitro and in vivo studies demonstrated that PDA–DOX/siPD-L1@SCM NPs showed excellent performance in synergistic chemoimmunotherapy for PCa bone metastases. Hence, this study provided an effective strategy for developing biomimetic multifunctional nanoparticles for PCa bone metastasis treatment.
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PubMed
高影响因子
Theranostics
·
2021
·
IF 11.556
Shi-Long Zhang,Yu-Qin Mao,Zheng-Yan Zhang,Zhan-Ming Li,Chao-Yue Kong,Hui-Ling Chen,Pei-Ran Cai,Bing Han,Tao Ye,Li-Shun Wang
Background: Anti-PD-1-based immunotherapy has emerged as a promising therapy for several cancers. However, it only benefits a small subset of colorectal cancer (CRC) patients. Mounting data supports the pivotal role of gut microbiota in shaping immune system. Pectin, a widely consumed soluble fiber, has been reported to ameliorate the imbalance of gut microbiota. Therefore, we aimed to explore the effect and the underlying mechanisms of pectin in improving anti-PD-1 mAb efficacy. Methods: The C57BL/6 mice were treated with a broad-spectrum antibiotic (ATB) cocktail to depleted endogenous gut microbiota and subsequently humanized with feces from healthy controls or newly diagnosed CRC patients. The antitumor efficacies of anti-PD-1 mAb combined with or without pectin were assessed using these mice. Flow cytometry and immunohistochemistry (IHC) were conducted to investigate the tumor immune microenvironment after treatment. The gut microbiota profiles and short-chain fatty acids (SCFAs) levels were determined by 16S ribosomal RNA (16S rRNA) gene sequencing and gas chromatography-mass spectrometry (GC-MS), respectively. The effect of gut microbiota on anti-PD-1 mAb efficacy after pectin supplement was further tested by fecal microbiota transplantation (FMT). Results: The anti-PD-1 mAb efficacy was largely impaired in the mice humanized with feces from newly diagnosed CRC patients compared to those from healthy controls. However, pectin significantly enhanced the anti-PD-1 mAb efficacy in the tumor-bearing mice humanized with CRC patient gut microbiota. Flow cytometry and IHC analysis revealed increased T cell infiltration and activation in the tumor microenvironment of mice treated with anti-PD-1 mAb plus pectin. In vivo depletion of CD8 + T cells diminished the anti-tumor effect of anti-PD-1 mAb combined with pectin. 16S rRNA gene sequencing showed that pectin significantly increased gut microbial diversity and beneficially regulated microbial composition. In addition, we identified unique bacterial modules that were significantly enriched in the anti-PD-1 mAb + pectin group, which composed of butyrate-producing bacteria indicative of good response to immunotherapy. Meanwhile, GC-MS showed that pectin altered the level of SCFA butyrate. Furthermore, butyrate, a main product of dietary fiber in gut microbial fermentation, was found to be sufficient to promote T cells infiltration and thus enhance the efficacy of anti-PD-1 mAb. In addition, FMT demonstrated the effects of pectin were dependent on gut microbiota. Importantly, the beneficial effects of pectin were confirmed in the mice humanized with gut microbiota from patient with resistance to anti-PD-1 mAb. Conclusion: Pectin facilitated the anti-PD-1 mAb efficacy in CRC via regulating the T cell infiltration in the tumor microenvironment, which was potentially mediated by the metabolite butyrate.
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PubMed
高影响因子
Small
·
2022
·Vol. 18
·期 13
·2107809
·
IF 15.153
Qinyanqiu Xiang,Chao Yang,Yuanli Luo,Fan Liu,Jun Zheng,Weiwei Liu,Haitao Ran,Yang Sun,Jianli Ren,Zhigang Wang
The efficacy of immune checkpoint inhibition in inducing death of cancer cells is affected by the immunosuppressive “cold” tumor microenvironment, which results in a poor response by the patient's antitumor immune system. However, the immunomodulatory effects of immunogenic cell death in response to irritation by heat energy and reactive oxygen species (ROS) can switch the tumor microenvironment from “cold” to “hot.” This study has developed a nanoadjuvant for immune therapy using iron tungsten oxide (FeWOx)-based nanosheets with surface PEGylation (FeWOx-PEG). This FeWOx-PEG nanoadjuvant serves as a chemodynamic reagent via the Fenton reaction and acts as a photosensitizer for photodynamic and photothermal therapy under near-infrared II laser irradiation; however, it could also be used to augment tumor-infiltrating T-cells and provoke a systemic antitumor immune response by combining the immunogenic cell death triggered by ROS and photothermal therapy with the immune checkpoint blockade. This research demonstrates that application of the FeWOx-PEG nanoadjuvant under the guidance of magnetic resonance/computed tomography/photoacoustic imaging can eliminate the primary tumor and suppress the growth of distant tumors.
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PubMed
高影响因子
DALTON TRANSACTIONS
·
2022
·Vol. 51
·期 33
·12604-12619
·
IF 4.569
Zuojie Li,Linming Li,Wenhuan Zhao,Bin Sun,Zhifang Liu,Min Liu,Jun Han,Zhengping Wang,Dacheng Li,Qingpeng Wang
To develop new anti-metastasis chemotherapeutic drugs, a series of flurbiprofen (FLP) and zaltoprofen (ZTP) platinum(IV) complexes targeting COX-2, PD-L1 and DNA was prepared and investigated. Complex 2 with dual FLP ligands displays promising antitumor activities in vitro and exhibits much potential in overcoming drug resistance. More importantly, the antitumor evaluation in vivo demonstrates that complex 2 possesses promising inhibition of cancer growth and metastasis simultaneously. Further investigation of the mechanism revealed the multi-specific antitumor function of complex 2. It exerts remarkable DNA damage after reduction to platinum(II) complex, and up-regulates the expression of p53 and γ-H2AX. Then, complex 2 promotes mitochondria-mediated apoptosis effectively by activating the Bcl-2/Bax/caspase3 pathway. Furthermore, inflammation in tumor tissues is restrained by the suppression of enzymes COX-2, MMP-9, NLRP3 and caspase1, which would favor the inhibition of tumor metastasis. Moreover, compound 2 boosts T-cell immunity by restraining PD-L1 expression, and further improving the density of CD3+ and CD8+ T cells in tumor tissues.
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PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2020
·
IF 5.977
Tianjiao Meng,Ningzhao Shang,Anaclet Nsabimana,Huimin Ye,Huan Wang,Chun Wang,Yufan Zhang
MicroRNA-21 (miR-21) has been widely investigated as important biomarkers for cancer diagnosis and treatment. Herein, a highly sensitive nonenzymatic electrochemical biosensor based on [email protected] frameworks ( [email protected] ) and target-catalytic hairpin assembly (CHA) with target recycling approach has been proposed for the detection of miR-21. The proposed biosensor integrates the efficient CHA strategy and excellent electrocatalytic performance of [email protected] nanocomposites. The concentration of miRNA-21 is related to the amount of the adsorbed electrocatalyst , leading to the different electrochemical signals for readout towards paracetamol (AP). This biosensor shows a low limit of detection of 0.713 fM with the dynamic range of 20 fM −600 pM under the optimal experimental conditions, providing a powerful platform for detecting miR-21. Furthermore, the designed biochemical self-assembly strategy of this electrochemical biosensor is promising candidate for potential applications in the analysis of other important genetic biomarkers for early diagnosis of cancers.
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PubMed
高影响因子
ENERGY & FUELS
·
2024
·
IF 5.2
Yanbin Zhang,Xifei Yin,Chenghu Zhang,Ying Li,Yinghui Sun,Jie Bai
Dry reforming of methane (DRM) provides an effective method for converting the two main greenhouse gases to hydrogen and carbon monoxide. In this work, Co-CeO2 and CoM-CeO2 (M = Ru, Pd, Pt) catalysts prepared by electrospinning technology were used for DRM. Due to the excellent catalytic performance of Pt itself, the CoPt-CeO2 catalyst had the highest DRM catalytic performance at 850 °C, with a methane (CH4) conversion of 94.12%, and remained stable in 24 h stability testing with almost no carbon deposition. The surface properties of the samples were characterized by Brunauer–Emmett–Teller (BET), temperature programmed reduction with H2 (H2-TPR), temperatureprogrammed desorption of CO2 (CO2-TPD), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The results indicated that part of the reason for the excellent catalytic performance exhibited by adding noble metals to the catalyst is closely related to the high dispersion of active metals. More importantly, the addition of noble metals significantly increased the medium and strong alkaline sites of the catalysts. The abundant oxygen vacancies in CeO2 itself and the increased alkaline sites of noble metals were conducive to the CO2 adsorption and dissociation and the oxidation of deposited carbon. Moreover, the addition of noble metals promoted the interaction between the active metal and support. The results of this study provide a reference for the design of high-performance Co-based DRM catalysts.
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高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2019
·
IF 7.65
Jaehyeong Park,Sungjun Bae
In this study, a magnetically recyclable Pd catalyst was developed by using the novel support of iron-rich coal fly ash/silica (IRFA@SiO 2 ) for highly efficient reduction of p -nitrophenol ( p -NP). IRFA microspheres were coated with amorphous SiO 2 synthesized from non-magnetic coal fly ash (NMFA) and then loaded with Pd by impregnation method for the synthesis of Pd/IRFA@SiO 2 . Various surface analyses demonstrated that amorphous SiO 2 was well deposited on the surface of IRFA, providing a unique three-dimensionally structured SiO 2 layer to suppress aggregation of IRFA and enhance dispersion of Pd nanoparticles. Pd/IRFA@SiO 2 exhibited a significantly enhanced p -NP reduction than those of Pd/IRFA, Pd/Al 2 O 3 , and Pd/SiO 2 . Compared to other Pd- and metal-loaded catalysts, Pd/IRFA@SiO 2 showed ˜4000× enhancements in k obs-p-NP /C M (L min −1 g M −1 , M = precious metals) values and ˜3800× increases in price-normalized k obs-p-NP values, indicating that Pd/IRFA@SiO 2 is a highly efficient and cost-effective alternative catalyst. The catalyst was successfully recycled five times without significant leaching of Pd, Si, and heavy metals because of the magnetic property of Pd/IRFA@SiO 2 . The experimental results suggest the applicability of the surface-modified IRFA support for the development of novel magnetically recoverable catalysts without severe toxicity problems.
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高影响因子
MICROCHIMICA ACTA
·
2010
·Vol. 168
·期 3
·347-354
·
IF 2.648
Qian Ping,Ai Shiyun,Yin Huanshun,Li Jinhuan
Au-Pd bimetallic nanoparticles were prepared in the presence of an amine-terminated dendrimer of a fourth generation poly(amidoamine) type. A biosensor was fabricated by immobilizing dsDNA on a thin layer of a dendrimer-encapsulated bimetallic nanoparticles (Au-Pd) in a chitosan composite on a glassy carbon electrode. The biosensor was evaluated by square wave voltammetry for the determination of the oxidative damage of immobilized DNA and the antioxidant capacity of sericin. The biosensor is shown to be suitable for the rapid detection of DNA damage and the assessment of the antioxidant capacity of sericin.
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高影响因子
NEW JOURNAL OF CHEMISTRY
·
2015
·Vol. 39
·期 6
·4519-4525
·
IF 3.086
Yansheng Liu,Xinlin Li,Xuanduong Le,Wei Zhang,Hao Gu,Ruiwen Xue,Jiantai Ma
MCM-48 mesoporous microspheres (M48N) with a pore size of 3.77 nm, an ultra-high surface area of 1250.77 m2 g−1 and a super-large pore volume of 1.52 cm3 g−1 were synthesized. The M48N microspheres were then modified with Pd, Pt and Ru nanoparticles using an incipient wetness impregnation technique. The modified M48N microspheres were investigated to determine their catalytic effect in the aqueous phase hydro-dechlorination (HDC) of 4-chlorophenol. The Pd–M48N, Pt–M48N and Ru–M48N catalysts were characterized by transmission electron microscopy, X-ray diffraction, nitrogen adsorption–desorption and X-ray photoelectron spectroscopy. The HDC experiments were performed using the fairly mild conditions of room temperature and an atmospheric pressure of H2. Pd–M48N showed a higher catalytic performance than Pt–M48N and Ru–M48N and various other Pd-based catalysts. The high catalytic performance of Pd–M48N resulted from the ultra-high surface area, super-large pore volume and unique pore structure of the M48N, which improved the mass transfer and increased the rate of adsorption–desorption of the compounds. This method has potential applications in the treatment of industrial wastewaters contaminated with chlorinated organic compounds.
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高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2018
·
IF 6.434
Jiafeng Ding,Gaoyuan Long,Yang Luo,Runze Sun,Mengxia Chen,Yajun Li,Yanfang Zhou,Xinhua Xu,Weirong Zhao
Polychlorinated dibenzo- p -dioxins (PCDDs), as a group of notorious anthropogenic environmental toxicants, are arguably ubiquitous in nature. In this study, we investigated the photocatalytic reductive dechlorination of 2-chlorodibenzo- p -dioxin (2-CDD) over Pd/g-C 3 N 4 catalysts under UV–vis irradiation. The g-C 3 N 4 and a series of Pd/g-C 3 N 4 catalysts were prepared by thermal polymerization and mechanical mixing-illumination method and characterized by XRD, TEM, BET, SEM and UV–vis DRS analyses. Among all the samples, the Pd/g-C 3 N 4 (5 wt%) yielded the optimal dechlorination activity with a total 2-CDD conversion of 54% within 4 h, and 76% of those converted 2-CDD were evolved to dibenzo- p -dioxin (DD). The kinetics of dechlorination could be described as pseudo-first-order decay model (R 2 > 0.84). Corresponding rate constants (k) increased from 0.052 to 0.17 h −1 with Pd contents up to 5 wt% and decreased to 0.13 h −1 with a 10 wt% of Pd. The enhanced activities originated from the surface plasmonic resonance (SPR) effect of Pd nanoparticles and the formation of Schottky barrier between Pd and g-C 3 N 4 , which extend the spectrum responsive range and suppress the charge recombination of g-C 3 N 4 . This is the first report on the photocatalytic reductive removal of PCDDs and may provide a new approach for PCDDs pollution control.
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高影响因子
INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
·
2022
·
IF 7.139
Ying Duan,Pan Guo,Dong Sui,Dongsheng Deng,Tianliang Lu,Yanliang Yang
The development of a cost-effective catalyst for hydrogen evolution from ammonia borane is of importance for the application of AB as a hydrogen storage material. In this manuscript, a series of noble metal catalysts M@CuOx/C (M = Ru, Rh, Pd, and Pt) are prepared by the galvanic reduction method. The catalysts are characterized by XRD , TEM , EDS mappings and lines scanning, XPS , HAADF-STEM, and ICP-OES. The noble metal is highly dispersed on the surface of Cu nanoparticles . The morphology of Cu nanoparticles changed according to different metals after the introduction of noble metal and there has an interaction between the noble metal and Cu. The M@CuOx/C is used for the hydrolysis of AB. For the same metal catalyst, the activity of M@CuOx/C is increased by about 3–7 times than the corresponding M/C at 298 K. The Rh shows the highest TOF and lowest activation energy among the four noble metals.
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高影响因子
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