BIOMATERIALS
·
2022
·
IF 15.304
Lei Cao,Huixiang Tian,Man Fang,Zhe Xu,Dongsheng Tang,Juan Chen,Jiye Yin,Haihua Xiao,Kun Shang,Hongbin Han,Xiangping Li
cGAS-STING pathway, as an essential intracellular immune response pathway, has attracted much attention in tumor immunotherapy. However, low metabolic stability of conventional STING agonists limits their clinical application. Recent study shows that chemotherapeutic drugs cisplatin and camptothecin (CPT) can activate cGAS-STING pathway and induce immune response by DNA damage. Nevertheless, the ability of chemotherapeutic drugs to activate STING is so weak that new strategies are required to improve drug delivery efficiency for enhanced DNA damage, and then efficiently activate cGAS-STING pathway. Herein, we have developed a hybrid platinum prodrug (CPT-Pt (IV)) which can be triggered to release cisplatin and CPT in tumor cells. CPT-Pt (IV) with high hydrophobicity is further self-assembled with a ROS sensitive polymer (P1) and mPEG 2k -DSPE into ROS responsive nanoparticles (NPs). NPs could accumulate in the tumor site to release cisplatin and CPT, resulting in DNA double damage and finally activating cGAS-STING pathway, inducing DC cells maturation and increasing tumor infiltration of CD8 + T cells on colorectal cancer mouse model. This study showed that common DNA targeted drugs can activate the cGAS-STING pathway in situ via nano delivery system, and enhance the effect of chemotherapy and immunotherapy, which provide a new strategy for clinical antitumor therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2022
·
IF 7.425
Yuwan Liu,Xiaojing Li,Shangyuan Sang,David Julian McClements,Long Chen,Jie Long,Aiquan Jiao,Jinpeng Wang,Xueming Xu,Zhengyu Jin,Chao Qiu
In this study, soybean peptide-succinic acid-modified cyclodextrin (SPT-SACD) nanoparticles (NPs) were successfully fabricated by combining SPT and SACD using an antisolvent precipitation approach. The effects of the average molecular weight of SPT and the SPT/SACD mass ratio on the structure and properties of the SACD-SPT NPs were investigated. Under optimal conditions, the SPT/SACD mass ratio was 2:1, and the SPT average molecular weight was 300 Da. SPT-SACD NPs were prepared under these conditions were spherical and had good uniformity. The particle sizes by DLS of SPT 1 (300 Da) /SACD and SPT 2 (500 Da) /SACD were in the range of 250–400 nm. The interaction between α-amylase and SPT-SACD NPs was investigated using ultraviolet visible (UV–Vis) absorption, fluorescence, and circular dichroism (CD) spectroscopy. The results of the fluorescence spectra and CD spectroscopy suggested that the presence of SPT-SACD NPs changed the microenvironment of the aromatic amino acid residues, which leads to the change of enzyme protein structure. The SPT-SACD NPs statically quenched the intrinsic fluorescence of the α-amylase by forming a complex with the enzyme. Moreover, the SPT-SACD NPs significantly improved the inhibitory effect of EGCG on α-amylase. The semi-inhibitory concentration (IC 50 ) decreased from 0.324 to 0.248 mg/mL. This study provides an improved understanding of the interaction mechanism between polypeptide-cyclodextrin complexes and digestive enzymes, which may facilitate the design of functional foods.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Communications
·
2022
·
IF 3.662
Chenghao Zhang,Chun Li,Mushi Zheng,Xiaoqing Si,Dejun Gao,Junlei Qi,Jian Cao
Ag nanoparticle paste was used to fabricate mechanically durable superhydrophobic surfaces via sintering. A facile method was first adopted to synthesize the Ag nanoparticle paste. To obtain multi-level hierarchical superhydrophobic surfaces, a stainless steel mesh was introduced to the sintering process of the Ag nanoparticle paste. The morphology of the steel mesh was replicated onto the Ag surface under sintering pressure, forming a first-level surface roughness . Using low-temperature sintering, a bond was created between the Ag nanoparticles, enhancing the mechanical durability of the as-prepared surfaces. The gap between the Ag nanoparticles was retained under low pressure, leading to a high surface roughness, which is beneficial for preparing superhydrophobic surfaces. After modification with stearic acid, the as-fabricated Ag coatings exhibited good superhydrophobicity, long-term durability, and mechanical stability. The superhydrophobic Ag coatings can also be fabricated on different substrates successfully. Thus, this type of superhydrophobic coating has promising prospects in practical applications.
✓ 已验证
产品关联
DOI
高影响因子
CANCER SCIENCE
·
2022
·
IF 6.518
Jie Liu,Huxia Wang,Miao Zhang,Yazhao Li,Ruiqi Wang,He Chen,Bo Wang,Xiaoqian Gao,Shaoran Song,Yaochun Wang,Yu Ren,Juan Li,Peijun Liu
Multiple cancers have been reported to be associated with angiogenesis and are sensitive to anti‐angiogenic therapies. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. However, the underlying anticancer mechanisms of antiangiogenic drugs are still unknown. Metformin (MET) and simvastatin (SVA), two metabolic‐related drugs, have been shown to play important roles in modulating the hypoxic tumor microenvironment and angiogenesis. Whether the combination of MET and SVA could exert a more effective antitumor effect than individual treatments has not been examined. The antitumor effect of the synergism of SVA and MET was detected in mouse models, breast cancer patient‐derived organoids, and multiple tumor cell lines compared with untreated, SVA, or MET alone. RNA sequencing revealed that the combination of MET and SVA (but not MET or SVA alone) inhibited the expression of endothelin 1 (ET‐1), an important regulator of angiogenesis and the hypoxia‐related pathway. We demonstrate that the MET and SVA combination showed synergistic effects on inhibiting tumor cell proliferation, promoting apoptosis, alleviating hypoxia, decreasing angiogenesis, and increasing vessel normalization compared with the use of a single agent alone. The MET and SVA combination suppressed ET‐1‐induced hypoxia‐inducible factor 1α expression by increasing prolyl hydroxylase 2 (PHD2) expression. Furthermore, the MET and SVA combination showed a more potent anticancer effect compared with bosentan. Together, our findings suggest the potential application of the MET and SVA combination in antitumor therapy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED SURFACE SCIENCE
·
2022
·
IF 7.392
Wei Zhang,Xue Guan,Xiao Qiu,Tonghuan Gao,Wanying Yu,Mengyuan Zhang,Liru Song,Dan Liu,Jidong Dong,Zaixing Jiang,Dawei Zhang
In this paper, skin-inspired multilayer Janus composite nanofibrous membranes with superhydrophilicity and superhydrophobicity as a wound dressing were designed and prepared to manage and utilize the exudates. Wettability, morphology, in-vitro release, cytotoxicity, antimicrobial activity and healing effect were investigated. Animal experiment and histological analysis confirmed the composite membranes were more effective in improving the healing of full-thickness defect wound, the growth of collagen fibers and collagen deposition. The four-layer composite membranes include the drug-loading layer containing Ciprofloxacin (CIP) and Astaxanthin (ATX) with superhydrophilic surface for self-pumping and drugs backflow, the hydrophobic polyvinylidene fluoride layer for delaying the exudates loss, and the superhydrophobic coating with self-cleaning properties for avoiding adhesion of foreign microorganisms. The exudates were absorbed into the composite membrane and locked in the nanofiber network to avoid dehydration of the wound, meanwhile, CIP and ATX were delivered to the wound bed to effectively inhibit bacterial growth and stimulate tissue regeneration. These results demonstrate that skin-inspired Janus composite nanofibrous membrane is a promising wound dressing for promoting full-thickness skin defect wound healing, displaying its great potential applications in skin tissue engineering.
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 20
·6929
·
IF 4.927
Lei Yang,Mohammad Javad Afshari,Jianxian Ge,Dandan Kou,Lei Chen,Dandan Zhou,Cang Li,Shuwang Wu,Leshuai Zhang,Jianfeng Zeng,Jian Zhong,Roland H. Stauber,Mingyuan Gao
Hypoxia is a common biological condition in many malignant solid tumors that plays an imperative role in regulating tumor growth and impacting the treatment’s therapeutic effect. Therefore, the hypoxia assessment is of great significance in predicting tumor development and evaluating its prognosis. Among the plenty of existing tumor diagnosis techniques, magnetic resonance imaging (MRI) offers certain distinctive features, such as being free of ionizing radiation and providing images with a high spatial resolution. In this study, we develop a fluorescent traceable and hypoxia-sensitiveT1-weighted MRI probe (Fe3O4-Met-Cy5.5) via conjugating notable hypoxia-sensitive metronidazole moiety and Cy5.5 dye with ultrasmall iron oxide (Fe3O4) nanoparticles. The results of in vitro and in vivo experiments show that Fe3O4-Met-Cy5.5 has excellent performance in relaxivity, biocompatibility, and hypoxia specificity. More importantly, the obvious signal enhancement in hypoxic areas indicates that the probe has great feasibility for sensing tumor hypoxia viaT1-weighted MRI. These promising results may unlock the potential of Fe3O4nanoparticles asT1-weighted contrast agents for the development of clinical hypoxia probes.Keywords:tumor hypoxia;ultrasmall iron oxide nanoparticles;magnetic resonance imaging;metronidazole
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2022
·
IF 7.425
Wen-Juan Pan,Lu-Lu Shi,Yu-Ru Ren,Cheng-Ying Yao,Yong-Ming Lu,Yan Chen
Age-associated increase in intestinal permeability is known to relate with gut microbiota dysbiosis and loss of epithelial tissue integrity. To improve healthy aging and prevent age-associated chronic disabilities, the protective potential of polysaccharides from Oudemansiella raphanipes (ORP-1) against age-associated intestinal epithelial barrier dysfunction in d -galactose-induced Caco-2 cells monolayer was investigated. In-vitro results demonstrated that ORP-1 can restore a healthy gut microbial population to handle age-related gut microbiota dysbiosis mainly by facilitating the proliferation and adhesion of probiotics Lactobacillus acidophilus ( L. acidophilus ) and Bifidobacterium bifidum ( B. bifidum ) to compete with intestinal pathogenic Escherichia coli ( E. coli ) for ecological niches and nutrition. Meanwhile, ORP-1 strengthened the intestinal structural integrity primarily by abolishing the aggravation of apoptosis and the age-associated alterations of tight junction (TJ) proteins expression in intestine. These findings highlighted that ORP-1 could be a potential functional food component with preventive utility against age-associated intestinal barrier injury.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Asian Journal of Pharmaceutical Sciences
·
2022
·
IF 9.273
Gaofeng Shu,Lin Shen,Jiayi Ding,Junchao Yu,Xiaoxiao Chen,Xiaoju Guo,Enqi Qiao,Yaning Chen,Chenying Lu,Zhongwei Zhao,Yongzhong Du,Minjiang Chen,Jiansong Ji
The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma (HCC). Here, a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin (FMPDA/Gd 3+ /DOX) was prepared as an effective theranostic agent for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of HCC. It was found that FMPDA/Gd 3+ /DOX had a high photothermal conversion efficiency of 33.4% and excellent T 1 −MRI performance with a longitudinal relaxivity (r 1 ) value of 14.966 mM −1 · s − 1 . Moreover, the results suggested that FMPDA/Gd 3+ /DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells, which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors. The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd 3+ /DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality. Overall, our study demonstrated that FMPDA/Gd 3+ /DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Yuanyuan Cai,Tao Dong,Xin Zhang,Aihua Liu
To regulate nanostructure synthesis is of crucial importance for developing various applications, including catalysis, bioanalysis, and optical devices. Herein, the morphology and peroxidase (POD)-mimicking activity of peptide-templated copper nanoassemblies (Cu NAs) are regulable with peptide types. The Cu NAs templated with peptide containing single cysteine are uniform nanoclusters with strong POD-like activity. However, the Cu NAs templated with peptide containing two cysteines are fusiform-like with very weak POD-like activity. Unexpectedly, the POD-like activity of Cu NAs templated with peptide containing two cysteines with lysine between the cysteines is significantly enhanced when trypsin is incubated, which is unchanged for the Cu NAs templated with peptide containing two cysteines without lysine between the cysteines. The remarkably enhanced POD-mimicking activity originates from trypsin specifically shearing the peptide bond on the lysine, thereby allowing the aggregated Cu NAs to unravel into individual nanoclusters. Therefore, a robust colorimetric sensing platform was constructed for sensitive and selective detection of trypsin, which showed a linear concentration range of 3–1000 nM and a detection limit of 0.82 nM (S/N = 3). More interestingly, featured by trypsin inhibitor restraining trypsin activity, it enabled us to screen trypsin inhibitors as well. Subsequently, the developed assay was applied to detect trypsin in serum samples with good accuracy and reproducibility. Thus, this strategy shows great potential application in the clinic for diagnosis of trypsin-indicating diseases as well as the screening of trypsin inhibitor-based anti-cancer drugs.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2022
·
IF 5.999
Jiayin Lin,Gang Li,Ke Jiang,Tao Xu,Chang Liu,Lipin Wang,Xu Zhang,Defu Cai,Chao Wu,Xianshi Meng,Wenquan Zhu
Recently, the therapeutic effect of chemotherapy has been obviously impaired due to premature drug release, low tumor penetration, and multidrug resistance of nanoplatforms. In this paper, a novel multiple-sensitive drug delivery system (MC-ss-CDs) was developed by gating long-wavelength emitting carbon dots (CDs) on the openings of mesoporous carbon nanoparticles (MC) through disulfide bonds. The MC with excellent photothermal transition efficiency and high drug storage capacity for doxorubicin (DOX) was used as the delivery carrier. The CDs had multiple functions, including intelligent switching to hinder unwanted release, photothermal therapy (PTT) agents to improve the heat generation effect of MCs and bioimaging trackers to monitor drug delivery. The disulfide bonds, as the linkers between MC carriers and CDs, are stable under normal physical conditions and relatively labile under high GSH concentrations in the cytoplasm of tumor cells. After arriving at the tumor microenvironment, DOX/MC-ss-CDs can rapidly break into DOX/MC and CDs under high GSH concentrations. DOX/MC could realize efficient integration of PTT and chemotherapy on the surface of the tumor by stimuli-responsive DOX release and synergetic heating of MC and CDs. The small-sized CDs with excellent penetrating ability could effectively enter the deep tumor and realize NIR-triggered photothermal ablation. The DOX/MC-ss-CDs showed a chemophotothermal effect with a combination index of 0.38 in vitro and in vivo . Therefore, the DOX/MC-ss-CDs could be employed as a trackable nanovehicle for synergistic chemotherapy and PTT at different depths.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Kun Ren,Ruijie Wang,Shinuo Fang,Shumeng Ren,Huiming Hua,Dongmei Wang,Yingni Pan,Xiaoqiu Liu
Ethnopharmacological relevance As a traditional Chinese medicine , Euodiae Fructus (EF) has been used to treat stomachache, belching, and emesis for more than a thousand years. Ancient records and modern research have shown that EF has mild toxicity, which needs to be processed with licorice juice to reduce its toxicity. Research suggested that the toxicity of EF can be caused by in vivo metabolism , but whether its metabolites are related to hepatotoxicity and whether licorice can affect the metabolism of EF have not been reported, which needed an effective strategy to clarify the correlation between metabolites and toxicity and the attenuation mechanism of licorice processing. Aim of the study The poisonous substances and metabolic pathways were clarified by comparing the mechanism in vivo process of the main alkaloids of EF in normal rats and rats treated with dexamethasone (DXMS), ketoconazole (KTC), and EF processed with licorice (EFP). Materials and methods Rats were given EF and EFP by oral administration, respectively. The EF + DXMS and EF + KTC groups were pretreated with DXMS and KTC, respectively, by i. p. for seven days, and their toxicity differences were compared. The comprehensive strategy based on UPLC-Q-Exactive-MS and Orthogonal Partial Least Squares Discriminant Analysis was developed to compare the types and contents of metabolites and clarify the metabolic pathways of alkaloids among EF, EFP, EF + KTC, and EF + DXMS groups. Results EF + DXMS group significantly increased the hepatotoxicity, whereas the EF + KTC and EFP groups reduced the hepatotoxicity compared with the EF group. One hundred and thirty-five metabolites were detected, and the metabolic pathways of the main alkaloid components related to toxicity were inferred in the plasma, urine, feces, and bile of rats. KTC and licorice similarly inhibited the production of toxic metabolites, changed metabolism in vivo, and produced many new II and a few phases I metabolites, while the contents of toxic metabolites increased in the DXMS group. Conclusion Licorice and KTC could inhibit the production of metabolites of EF related to toxicity, increase the production of other metabolites and promote the excretion of alkaloids, which may be why licorice and KTC can minimize EF toxicity.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Research
·
2022
·Vol. 26
·期 1
·1-21
·
IF 15.863
Wu Hao,Wei Guoli,Luo Lixia,Li Lingchang,Gao Yibo,Tan Xiaobin,Wang Sen,Chang Haoxiao,Liu Yuxi,Wei Yingjie,Song Jie,Zhang Zhenhai,Huo Jiege
Background Combination of chemotherapy and immune checkpoint inhibitor therapy has greatly improved the anticancer effect on multiple malignancies. However, the efficiency on triple-negative breast cancer (TNBC) is limited, since most patients bear “cold” tumors with low tumor immunogenicity. Doxorubicin (DOX), one of the most effective chemotherapy agents, can induce immunogenic cell death (ICD) and thus initiating immune response.Methods In this study, to maximize the ICD effect induced by DOX, chitosan and cell-penetrating peptide (R6F3)-modified nanoparticles (PNPs) loaded with ginsenoside Rg3 (Rg3) were fabricated using the self-assembly technique, followed by co-encapsulation with DOX based on thermo-sensitive hydrogel. Orthotopic tumor model and contralateral tumor model were established to observe the antitumor efficacy of the thermo-sensitive hydrogel combined with anti-PD-L1 immunotherapy, besides, the biocompatibility was also evaluated by histopathological.Results Rg3-PNPs strengthened the immunogenic cell death (ICD) effect induced by DOX. Moreover, the hydrogel co-loading Rg3-PNPs and DOX provoked stronger immune response in originally nonimmunogenic 4T1 tumors than DOX monotherapy. Following combination with PD-L1 blocking, substantial antitumor effect was achieved due to the recruitment of memory T cells and the decline of adaptive PD-L1 enrichment.Conclusion The hydrogel encapsulating DOX and highly permeable Rg3-PNPs provided an efficient strategy for remodeling immunosuppressive tumor microenvironment and converting immune “cold” 4T1 into “hot” tumors.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）