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Pharmaceutics · 2024 ·Vol. 16 ·期 6 ·833 · IF 4.9

Personalized SO2 Prodrug for pH-Triggered Gas Enhancement in Anti-Tumor Radio-Immunotherapy

Zhiran Chen,Xiaoxiang Zhou,Bo Wu,Han Tang,Wei Wei,Daoming Zhu,Yi Ding,Longyun Chen

The inhibition of the immune response in the tumor microenvironment by therapy regimens can impede the eradication of tumors, potentially resulting in tumor metastasis. As a non-invasive therapeutic method, radiotherapy is utilized for tumor ablation. In this study, we aimed to improve the therapeutic impact of radiotherapy and trigger an immune response by formulating a benzothiazole sulfinate (BTS)-loaded fusion liposome (BFL) nanoplatform, which was then combined with radiotherapy for anti-cancer treatment. The platelet cell membrane, equipped with distinctive surface receptors, enables BFL to effectively target tumors while evading the immune system and adhering to tumor cells. This facilitates BFL’s engulfment by cancer cells, subsequently releasing BTS within them. Following the release, the BTS produces sulfur dioxide (SO2) for gas therapy, initiating the oxidation of intracellular glutathione (GSH). This process demonstrates efficacy in repairing damage post-radiotherapy, thereby achieving effective radiosensitization. It was revealed that an immune response was triggered following the enhanced radiosensitization facilitated by BFL. This approach facilitated the maturation of dendritic cell (DC) within lymph nodes, leading to an increase in the proportion of T cells in distant tumors. This resulted in significant eradication of primary tumors and inhibition of growth in distant tumors. In summary, the integration of personalized BFL with radiotherapy shows potential in enhancing both tumor immune response and the elimination of tumors, including metastasis.

研究领域: 癌症治疗 · 纳米技术 · 免疫疗法 · 放射治疗 · 药学
✓ 已验证 DOI PubMed 高影响因子
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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE · 2024 · IF 4.2

PTPN2 dephosphorylates STAT3 to ameliorate anesthesia-induced cognitive decline in aged rats by altering the microglial phenotype and inhibiting inflammation

Xiaochun Zhao,Xueting Wang,Ziyang Xu,Xiaohan Chang,Yue Tian

Perioperative neurocognitive disorders (PNDs) are common neurological complications after anesthesia in the elderly. Protein tyrosine phosphatase non-receptor type 2 (PTPN2) regulates signal transducer and activator of transcription protein 3 (STAT3) signaling to control inflammation in certain organs, but its role in PNDs remains unknown. Herein, we constructed a PND model in 18-month-old rats by treating them with sevoflurane. PND rats developed neuroinflammation, along with a significant decrease in PTPN2 expression and a rise in STAT3 phosphorylation in the hippocampus. Ptpn2 overexpression alleviated the behavioral disorders of PND rats, ameliorated neuronal injury, inhibited neuroinflammation, inflammasome activation, microglial activation, and microglial phenotype switching. Similar results were observed in sevoflurane-treated HMC3 microglia with PTPN2 overexpression, while PTPN2 silencing showed the opposite results. Additionally, PTPN2 seems to be a target of T-box transcription factor 2 (TBX2). These results contribute to the evidence supporting the idea that PTPN2 is a regulatory factor in PND progression.

研究领域: 神经科学 · 药理学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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MICROCHIMICA ACTA · 2019 ·Vol. 186 ·期 3 ·1-8 · IF 5.479

A hybrid material composed of guanine-rich single stranded DNA and cobalt(III) oxyhydroxide (CoOOH) nanosheets as a fluorescent probe for ascorbic acid via formation of a complex between G-quadruplex and thioflavin T

Liu Shi Gang,Luo Dan,Han Lei,Li Nian Bing,Luo Hong Qun

A hybrid material composed of guanine-rich single stranded DNA (G-rich ssDNA) and cobalt oxyhydroxide (CoOOH) nanosheets is used as a nanoprobe for fluorometric turn-on detection of ascorbic acid (AA). The CoOOH nanosheets function as a recognition component for AA. The G-rich ssDNA is used to produce a G-quadruplex, and the G-quadruplex/thioflavin T (ThT) complex acts as a fluorescent reporter. In the absence of AA, p-phenylenediamine (PPD) is oxidized to form oxPPD which has a dark red color. It causes the fluorescence of the G-quadruplex/ThT complex to be quenched. However, in the presence of AA, the CoOOH nanosheets of the nanoprobe are preferentially reduced by AA. Hence, PPD is not oxidized, and fluorescence is not quenched. A fluorometric turn-on method was developed based on these findings. It has a detection limit of 94 nM and works in the concentration range from 1 to 10 and 20 to 80 μM. This method was applied to the determination of AA in (spiked) fruit juice samples. Schematic presentation of a fluorescent assay of ascorbic acid (AA) is established using a nanoprobe composed of guanine-rich single stranded DNA (G-rich ssDNA) and cobalt oxyhydroxide (CoOOH) nanosheets. It is based on competitive reduction of CoOOH by p-phenylenediamine (PPD) and AA. Thioflavine T (ThT) induces the formation of fluorescent G-quadruplex/ThT complex. The oxidized form of PPD (oxPPD) can quench the fluorescence via fluorescence resonance energy transfer (FRET), but AA suppresses quenching.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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NANOTECHNOLOGY · 2021 ·Vol. 32 ·期 42 ·425101 · IF 3.874

Moderating hypoxia and promoting immunogenic photodynamic therapy by HER-2 nanobody conjugate nanoparticles for ovarian cancer treatment

Qing Zhang,Lian Wu,Shaozheng Liu,Qingjie Chen,Lingpeng Zeng,Xuezhong Chen,Qing Zhang

Photodynamic therapy (PDT) and immunotherapy have been often adopted for ovarian cancer therapy, yet their application is limited by the high recurrence rate and toxic side effects. Intriguingly, nanoparticles contribute to enhancing the performance of PDT. Here, we investigated the synthesis of HER-2-Nanobody (Nb)-conjugated human serum albumin (HSA) incorporated with chlorin (Ce6) and catalase (CAT) (Nb@HCC), and analyzed the synergic effect of Nb@HCC-mediated PDT and immunotherapy for SK-OV-3 tumors. The Ce6 and CAT were incorporated into HSA to construct the HCC nanoparticles. HER-2-Nanobody was the purified bacterial crude extract, and conjugated with HCC to prepare Nb@HCC via heterodisulfide. The effects of Nb@HCC with near infrared ray (NIR) irradiation on moderating hypoxia and hypoxia inducible factor-1α (HIF-1α) expression were evaluated in the SK-OV-3 cells and tumor tissues. A SK-OV-3 tumor-bearing model was developed, where the synergistic effect of Nb@HCC-mediated PDT and anti-CTLA-4 therapy was investigated. Nb@HCC with a 660 nm laser irradiation could induce massive reactive oxygen species and trigger apoptosis in SK-OV-3 cells. Nb@HCC and PDT promoted danger-associated molecular patterns (DAMPs), which indicated immunogenic cell death and maturation of dendritic cells in the SK-OV-3 cells. Irradiated by NIR, Nb@HCC alleviated the hypoxia and decreased the expression of HIF-1α. The Nb@HCC-mediated PDT and anti-CTLA-4 therapy synergically inhibited the progression of distant tumor, and induced T cell infiltration. Biosafety tests suggested that Nb@HCC would not cause damage to the major organs with less toxicity and side effects. To conclude, a combination of Nb@HCC-mediated PDT and anti-CTLA-4 therapy could inhibit the progression of distant tumor to attain remarkable therapeutic outcomes.

研究领域: 肿瘤学 · 纳米技术 · 免疫治疗 · 药学
✓ 已验证 DOI PubMed 高影响因子
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Cancer Immunology Research · 2022 ·Vol. 10 ·期 4 ·525-539 · IF 12.02

CDK2 Inhibition Enhances Antitumor Immunity by Increasing IFN Response to Endogenous Retroviruses

Chen Yu,Cai Qiaomei,Pan Chaohu,Liu Wancheng,Li Lili,Liu Junxiao,Gao Meiling,Li Xiaorong,Wang Liguo,Rao Yu,Yang Heng,Cheng Genhong

Inhibitors of cyclin-dependent kinase-2 (CDK2) are commonly used against several solid tumors, and their primary mechanisms of action were thought to include cell proliferation arrest, induction of cancer cell apoptosis and induction of differentiation. Here, we found that CDK2 inhibition by either small molecular inhibitors or genetic Cdk2 deficiency promoted antitumor immunity in murine models of fibrosarcoma and lung carcinoma. Mechanistically, CDK2 inhibition reduced phosphorylation of RB protein and transcription of E2F-mediated DNA methyltransferase 1 (DNMT1), which resulted in increased expression of endogenous retroviral RNA and type I IFN (IFN-I) response. The increased IFN-I response subsequently promoted antitumor immunity by enhancing tumor antigen presentation and CD8 + T-cell infiltration. Our studies provide evidence that inhibition of CDK2 in cancer cells suppresses tumor growth by enhancing antitumor immune responses in the tumor microenvironment, suggesting a new mechanism to enhance antitumor immunity by CDK2 inhibitors.

研究领域: 肿瘤学 · 免疫学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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CARBOHYDRATE POLYMERS · 2020 · IF 7.182

Receptor and signaling pathway involved in bovine lymphocyte activation by Atractylodis macrocephalae polysaccharides

Wei Xu,Sijia Fang,Yong Wang,Xiaoqing Chi,Xiaodan Ma,Tao Zhang,Songhua Hu

The present study was to investigate the molecular mechanism underlying lymphocyte activation by total polysaccharides from Atractylodis macrocephalae (RAMPtp). The results showed that RAMPtp significantly promoted the secretions of cytokines (IFN-γ, IL-1α, IL-21, IFN-α, CCL4, CXCL9 and CXCL10), increased the proportions of CD4 + and CD8 + subpopulations, and enhanced the expressions of c-JUN, NFAT4, STAT1 and STAT3. microRNA sequencing identified 67 differentially expressed miRNAs (DEMs) in RAMPtp-stimulated SMLN lymphocytes, including 55 up-regulated and 12 down-regulated. GO and KEGG enrichment analyses of the predicted DEMs-targeted genes indicated that they were associated with immune system pathways, including PI3K-Akt, MAPKs, Jak-STAT and Calcium signaling pathways, which were confirmed by western blot and pathway inhibition assays. RAMPtp was further observed to favor immunostimulatory effect on both T and B lymphocytes via binding to TCR and membrane Ig individually. These findings might explain the immunomodulatory mechanism of RAMPtp in ameliorating the bovine intramammary infection.

研究领域: 免疫学 · 分子生物学 · 兽医学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2020 · IF 7.1

Integration of ion-tuned oligonucleotide structural motifs and DNA-templated copper nanoclusters as a manipulable logic device

Xiangli Shao,Longjiao Zhu,Yangzi Zhang,Zaihui Du,Chunyan Sun,Wentao Xu

Molecular logic gates possess great potential for multi-parameter sensing, intelligent diagnostics, and molecular computation. One remaining challenge was to construct novel new logic gates based on smart nanomaterials and functional nucleic acids. In this study, two novel new logic devices were constructed utilizing ion-tuned DNA/copper nanoclusters (CuNCs), which were dual-responsive to K + and H + . By merely altering the arrangement of a specific sequence of the DNA stabilizer, two kinds of well-designed DNA probes permuted by G-tracts, C-tracts, and poly-T were designed as the building blocks of the logic device. Poly-T acted as the template for the formation of CuNCs. G-tracts and C-tracts enabled a K + /H + -responsive conformational switch into G-quadruplex (G4) and i-motif structures. Such a conformational conversion significantly modulated the fluorescence behaviors of CuNCs. This study discovered the unique interaction between the logic device and graphene oxide (GO). The logic devices were implemented for the analysis of K + and microRNA.

研究领域: 纳米技术 · 生物化学 · 分子生物学 · 生物医学工程
✓ 已验证 DOI 高影响因子
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REACTIVE & FUNCTIONAL POLYMERS · 2018 · IF 2.975

Thermo- and pH-responsive copolymer poly(t-butyl acrylate)-b-poly{[2-(dimethylamino) ethyl methacrylate]-co-[poly(ethylene glycol) methyl ether methacrylate]}: Preparation, characterization, and their applications as organic dye adsorbents and drug delivery systems

Zhenglong Yang,Kangyu Fu,Jing Yu,Peiting Zhou,Zhihao Cheng

Temperature and pH double-response poly(t-butyl acrylate)- b -poly{[2-(dimethylamino) ethyl methacrylate]- co -[poly(ethylene glycol) methyl ether methacrylate]} (PtBA -b- P(DMAEMA- co -PEGMEMA)) were successfully prepared by RAFT polymerization and could be self-assembled into micelles . 1 H NMR, UV-vis absorbance and DLS measurements were used to characterize their structures and self-assembly behaviors. At the same time, the adsorption of organic dyes and the control of drug release were also introduced. The results showed that the critical micelle concentration of PtBA- b -P(DMAEMA- co -PEGMEMA) was 2.55 mg/L. As the value of pH increased from 2 to 11, their particle size decreased from 178 nm to 130 nm. PtBA- b -P(DMAEMA- co -PEGMEMA) was also temperature responsive, with the hydrophobic block grows, the temperature of the particle mutation would increase. Therefore, PtBA- b -P (DMAEMA- co -PEGMEMA) could control the transfer and release of organic dyes such as methyl red and dithizone through their pH-sensitive properties, and the process had good reversibility. Meanwhile, PtBA- b -P(DMAEMA- co -PEGMEMA) micelles could also deliver some specific hydrophobic anticancer drug , such as camptothecin (CPT). In conclusion, the copolymers synthesized in this work have potential applications in the fields of environmental protection and drug delivery.

✓ 已验证 产品关联 DOI 高影响因子
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Nano Research · 2024 · IF 9.5

A stepwise-responsive editor integrated with three copper ions for the treatment of oral squamous cell carcinoma

Ren Jinna,Hu Jingying,Dong Fan,Xu Yan,Peng Yang,Qian Yuping,Zhang Guanmeng,Wang Min,Wang Yuguang

Cuprotosis, a new type of cell death, provides great opportunities for the treatment of oral squamous cell carcinoma, as nanocarriers of copper ions can induce cuprotosis and immunogenic death. Here, we studied an editor that enables production of a nanoparticle “storm” in oral squamous cell carcinoma, maximizing the toxic effect of these particles and reprogramming the tumor microenvironment; as a result, T cells and natural killer (NK) cells can infiltrate the tumor microenvironment to activate an antitumor immune response. On this basis, the editor can be combined with optical therapy to improve patient prognosis. In this study, the metal ratio was regulated in response to the nanocarrier of acid response type. Thus, in the presence of a specific copper ion content, the nanocarrier could change the permeability of the tumor cell membrane. Based on these results, the nanoparticles were cracked in an acidic environment and then released copper ions. Finally, the nanoparticles contributed to cuprotosis and immunogenic death. In addition, the editor could inhibit murine oral cancer 1 (MOC1) tumors in C57BL/6 without toxicity. The rate of tumor growth inhibition was as high as approximately 80%. This strategy provides a new idea for immunotherapy. Moreover, it can improve the interaction between immunotherapy and the copper-induced death of oral squamous cell carcinoma. Above all, this study will provide a new opportunity for the effective treatment of oral squamous cell carcinoma.

研究领域: 肿瘤学 · 纳米技术 · 免疫疗法 · 细胞生物学
✓ 已验证 DOI 高影响因子
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JOURNAL OF CHEMICAL AND ENGINEERING DATA · 2010 · IF 1.695

Excess Molar Volumes of 1,3-Diethyl Propanedioate with Methanol, Ethanol, Propan-1-ol, Propan-2-ol, Butan-2-ol, 2-Methyl-propan-1-ol, and Pentan-1-ol at T = (288.15, 298.15, 313.15, and 328.15) K

Yihe Wang,Weidong Yan

Densities of binary mixtures of 1,3-diethyl propanedioate with methanol, ethanol, propan-1-ol, propan-2-ol, butan-2-ol, 2-methyl-propan-1-ol, and pentan-1-ol have been measured at temperatures of (288.15, 298.15, 313.15, and 328.15) K using an Anton Paar model DMA 5000 M oscillating densimeter. Excess molar volumes were calculated from these densities. The experimental data were fitted to the Redlich−Kister equation.

CAS / MDL: 78-83-1
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Nanophotonics · 2021 ·Vol. 10 ·期 12 ·3267-3278 · IF 8.449

Fe2P nanorods based photothermal therapy combined with immune checkpoint inhibitors for pancreatic cancer

Shanshan Liu,Jiawen He,Ruixiang Song,Mengmeng Zhang,Lianghao Huang,Jing Chen,Meng Wang,Fang Liu,Feifan Zhou

Treatment of pancreatic cancer is faced with great difficulties and challenges due to high lethality and metastasis. Synergism of targeted therapy and immunotherapy has been considered as ideal strategy to both eliminate primary tumors and control metastases. For the treatment of advanced pancreatic cancer, we demonstrated a local photothermal therapy (PTT) following administration of monoclonal antibody of programmed death ligand 1 (αPD-L1). Fe 2 P nanorods were employed as a Fenton agent and photothermal agent, which modified with DSPE-PEG 2000 -Mal for improved biocompatibility and Mal mediated-antigen presentation. Under a low dose laser irradiation at 980 nm, Fe 2 P-PEG-Mal nanorods (NRs) mediated PTT could induce immunogenic tumor cell death that can cause dendritic cells (DCs) infiltration and maturation. In a bilateral pancreatic tumor model, the local treatment of NRs-PTT on primary tumor could cause the increased infiltration of cytotoxic T lymphocytes (CTLs) and decreased residential of M2 macrophages in untreated distal tumors. Furthermore, subsequently intervened αPD-L1 could enhance cell death triggered by CTLs in distal tumors through reversing immunosuppression. An orthotopic pancreatic tumor model was used to further confirm the therapeutic outcome. Finally, the combination of NRs based PTT and αPD-L1 based immunotherapy was able to significantly eliminate orthotopic pancreatic tumors and reduce mesentery metastases. Thus, the strategy may provide a more effective treatment for pancreatic cancer.

研究领域: 肿瘤学 · 纳米技术 · 免疫疗法 · 生物医学工程
✓ 已验证 DOI 高影响因子
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INDUSTRIAL CROPS AND PRODUCTS · 2023 · IF 5.9

Solvent-free microwave extraction of essential oil and hydrosol from fresh leaves of Cinnamomum burmannii (Nees et T. Nees) Blume after screw extrusion treatment and evaluation of pancreatic lipase inhibitory activities in vitro compared to its main components

Zehao Wang,Ru Zhao,Hongfei Gao,Yang Yang,Xinyu Yang,Huiyan Gu,Lei Yang,Xiaonan Zhang,Tingting Liu

One of the most significant sources of commercial camphor oil is the essential oil of Cinnamomum burmannii (Nees et T. Nees) Blume leaves, which has been manufactured using a variety of distillation techniques, including hydrodistillation and microwave-assisted hydrodistillation. In this study, we employed solvent-free microwave extraction (SFME) to recover hydrosol and essential oil from fresh C. burmannii leaves that had undergone screw extrusion. An optimum yield of 12.35 ± 0.62 mL/kg DW of essential oil was obtained by optimizing the major SFME contributing parameters using a face-centered central composite design (FCCCD). By using SFME, the influence of microwave irradiation power on the yield and quality of the essential oil of fresh leaves of C. burmannii was examined. With the aid of first- and second-order kinetic equations, SFME was contrasted with hydrodistillation and dry distillation. A total of 32 components were detected in the essential oil, and 22 components were detected in the hydrosol obtained by SFME under the optimized conditions. The main components of the essential oil were 1,8-cineole (21.67%), borneol (17.37%) and α -terpineol (7.45%), in descending order, and the main components of the hydrosol were trans -2-hydroxycinnamic acid (21.45%), borneol (22.07%), 1,8-cineole (13.65%) and α -terpineol (11.93%). 1,8-Cineole and borneol were the two components with the highest influence on hierarchical clustering, according to principal component analysis and heatmap analysis. Moreover, box-whisker plots were used to determine and compare the inhibitory activities of the essential oil and its three primary constituents against pancreatic lipase . The outcomes demonstrated that 1,8-cineole played a critical role in the essential oil's ability to inhibit pancreatic lipase, and they also demonstrated a positive correlation between the concentration and the amount of inhibition activity.

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