Biomaterials Science
·
2024
·
IF 5.8
Yu Xia,Ming-Kang Zhang,Jing-Jie Ye,Mei-ting Niu,Xin-yi Dai,Zi-yang Wang,Zhi-ling He,Jun Feng
Metabolic disorders of cancer cells create opportunities for metabolic interventions aimed at selectively eliminating cancer cells. Nevertheless, achieving this goal is challenging due to cellular plasticity and metabolic heterogeneity of cancer cells. This study presents a dual-drug-loaded, macrophage membrane-coated polymeric nanovesicle designed to reprogram cancer metabolism with high specificity through integrated extracellular and intracellular interventions. This nanoformulation can target cancer cells and largely reduce their glucose intake, while the fate of intracellular glucose internalized otherwise is redirected at the specially introduced oxidation reaction instead of inherent cancer glycolysis. Meanwhile, it inhibits cellular citrate intake, further reinforcing metabolic intervention. Furthermore, the nanoformulation causes not only H2O2 production but also NADPH down-regulation, intensifying Redox damages to cancer cells. Consequently, this nanoformulation displays highly selective toxicity to cancer cells and minimal harms to normal cells mainly due to metabolic vulnerability of the former. Once administrated into tumor-bearing mice, this nanoformulation is found to induce the transformation of pro-tumor tumor associated macrophages into the tumor-suppressive phenotype and completely inhibit tumor growth with favourable biosafety.
研究领域:
癌症生物学
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纳米技术
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药物科学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2023
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IF 9.9
Yao Li,Mengying Liu,Yan Zheng,Zheng Wang,Yanjun Zhao
Cancer cells show unique redox homeostasis . Glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) play essential roles as coenzymes of multiple key antioxidant enzymes. Coenzyme depletion offers a unique opportunity for cancer treatment by inducing oxidative stress . Here, we report an innovative hybrid nanocarrier for cancer redox therapy via selective depletion of GSH and NADPH. The nanocarrier core is a sorafenib-loaded porous zeolitic imidazole framework (ZIF-65), and the shell is epigallocatechin gallate (EGCG)-Fe 3+ complex (EF). The nitroimidazole ligand in ZIF-65 could selectively deplete NADPH under hypoxia . Sorafenib diminished GSH by inhibiting cystine import and GSH biosynthesis. EGCG can reduce Fe 3+ to Fe 2+ , which aids the generation of hydroxyl radicals via the Fenton reaction . The reversible coordination between nitroimidazole and Zn 2+ , EGCG, and Fe 3+ enables triggered cargo release in acidic lysosomes . Tailored nanocarriers induced the depletion of both coenzymes (GSH and NADPH) and boosted reactive oxygen species in a 4T1 murine cancer cell line. The altered redox balance eventually resulted in efficient apoptotic cell death. The current work offers a novel means of redox cancer therapy via the selective depletion of key antioxidant enzymes in hypoxic cells.
研究领域:
癌症治疗
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纳米技术
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氧化还原生物学
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药学
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产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2020
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IF 7.1
Dongxue Sun,Tianli Liu,Yuming Dong,Qingyun Liu,Xiuming Wu,Guang-Li Wang
Herein, an innovative dehydrogenase invoked tri-enzyme cascade has been successfully constructed and utilized as a powerful and universal colorimetric strategy for dehydrogenase-based bioassays. Specifically, the glucose-6-phosphatedehydrogenase (G6PD) catalyzes the specific dehydrogenation of glucose-6-phosphate (G-6-P) by consuming the oxidized form of β-nicotinamide adenine dinucleotide phosphate (NADP + ) to generate NADPH. And the formed NADPH initiates the irreversible hydroxylation of p-hydroxybenzoate by p-hydroxybenzoate hydroxylase (PHBH) to generate 3,4-dihydroxybenzoate (DHB), which results in the subsequent in situ generation of a photoresponsive nanozyme of DHB coordinated SrTiO 3 (SrTiO 3 /DHB) nanosheets. The photoresponsive nanozyme has intriguing interfacial charge transfer (ICT) characteristics and thus realizes the efficiently catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) under light irradiation for signal readout. Exemplified by G6PD and G-6-P as analytes, the dehydrogenase invoked tri-enzyme cascade achieved efficient signal amplification towards the ultrasensitive colorimetric bioassays. This study opens up the ICT transitions of SrTiO 3 for innovative dehydrogenases-involved enzyme cascades. In addition, it is an entirely new method for dehydrogenases-based bioassays, with the distinctive merits of facile operation, rapid response, high sensitivity, and naked-eye readout. Importantly, it is extensible as a general basis for other numerous targets of interest because of the large numbers of dehydrogenases available for catalysing different reactions.
研究领域:
生物化学
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分析化学
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纳米技术
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生物催化
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产品关联
DOI
高影响因子
ADVANCED MATERIALS
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2022
·Vol. 34
·期 13
·2109726
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IF 32.086
Yuxiang Wang,Jing Chen,Rumeng Duan,Rong Gu,Weiran Wang,Jinhui Wu,Huibo Lian,Yiqiao Hu,Ahu Yuan
In situ tumor vaccination is preliminarily pursued to strengthen antitumor immune response. Immunogenic tumor cell death spontaneously releases abundant antigens and adjuvants for activation of dendritic cells, providing a paragon opportunity for establishing efficient in situ vaccination. Herein, Phy@PLGdH nanosheets are constructed by integrating physcion (Phy, an inhibitor of the pentose phosphate pathway (PPP)) with layered gadolinium hydroxide (PLGdH) nanosheets to boost radiation-therapy (RT)-induced immunogenic cell death (ICD) for potent in situ tumor vaccination. It is first observed that sheet-like PLGdH can present superior X-ray deposition and tumor penetrability, exhibiting improved radiosensitization in vitro and in vivo. Moreover, the destruction of cellular nicotinamide adenine dinucleotide phosphate (NADPH) and nucleotide homeostasis by Phy-mediated PPP intervention can further amplify PLGdH-sensitized RT-mediated oxidative stress and DNA damage, which correspondingly results in effective ICD and enhance the immunogenicity of irradiated tumor cells. Consequently, Phy@PLGdH-sensitized RT successfully primes robust CD8 + -T-cell-dependent antitumor immunity to potentiate checkpoint blockade immunotherapies against primary and metastatic tumors.
研究领域:
癌症研究
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放射肿瘤学
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免疫疗法
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纳米技术
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分子生物学
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DOI
PubMed
高影响因子
Journal of Environmental Chemical Engineering
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2024
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IF 7.4
Shuangshuang Li,Xin Jiang,Chi Zhao,Yuan Ren,Lixin Luo
Biosurfactants combined with bioaugmentation for the remediation of petroleum hydrocarbon-contaminated soils proved to be one of the most effective ways. However, research on lipopeptides combined with bioaugmentation is rare, and the biological mechanisms are undefined. Therefore, the effect of Raoultella planticola and the lipopeptides it produces to restore contaminated soils was investigated using n-hexadecane as a model of petroleum hydrocarbons. After 60 d, n-hexadecane removal rate increased from 31.3% in contaminated soil to 39.9% with R. planticola alone and 59.0% with R. planticola together with 1.0 g intracellular lipopeptide (INLS) and 7.5 g sodium gluconate (SG)/kg dry soil. Meanwhile, the nitrogen and phosphorus components of the soil increased by 13.9% and 8% in the experimental group, respectively. Besides, DHA activity was 6.7 times that of the control group at 28 d, indicating a considerable increase in DHA activity. Microbial community analysis revealed a considerable increase in functional genera of Sphingomonas , Nocardia , Pseudoalteromonas , Povalibacter , Apiotrichum , Pseudallecheria , and Ascodesmis . The amount of fungus in the experimental group was more than 30 times that of the control group after 60 d. Microbial co-occurrence networks showed improved interactions of Firmicutes and Ascomycota, encouraging synergistic cooperation among microbes and thereby accelerating n-hexadecane breakdown. At once, the metabolic pathways ko00071 and ko00980 for n-hexadecane degradation were greatly elevated, indicating that functional genes such as alkane 1-monooxygenase and NADPH-cytochrome P450 reductase were activated. These results implied that combining hydrocarbon-degrading microbial with INLS was a promising bioremediation technique to remove soil petroleum hydrocarbons.
研究领域:
环境科学
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微生物学
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生物技术
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土壤学
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产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
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2022
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IF 12.545
Xia Liu,Lei Qin,Jie Yu,Wentao Sun,Jianhong Xu,Chun Li
During industrial fermentation , microbial cell factories are usually confronted with environmental or metabolic stresses, leading to the imbalance of intracellular redox and the reduction of cell metabolic capacity. Here, we constructed the genetically encoded redox biosensor system (RBS) based on redox-sensitive fluorescent proteins to detect redox metabolites , including reactive oxygen species (ROS), oxidized glutathione , NADH, and NADPH in Saccharomyces cerevisiae . The functional biosensors were quantitatively characterized and the orthogonal redox biosensor system (oRBS) was designed for detecting multiple redox metabolites. Furthermore, the compartment targeted redox biosensor system (ctRBS) was constructed to detect ROS and NADPH, revealing the distribution and spatiotemporal dynamics of ROS in yeast under various stress conditions. As a proof-of-concept, RBS was applied to evaluate the redox states of engineered yeast with stress resistance and heterogenous triterpene synthesis in vivo , elucidating the redox balance significantly affecting the growth and production phenotypes. The RBS in this study allowed the exploration of the diversity of compartmental redox state and real-time monitoring of the production process of yeast, providing a reliable and effective approach for accurate and in-depth profiling of bottlenecks of yeast cell factories.
研究领域:
生物技术
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微生物学
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分子生物学
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系统生物学
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产品关联
DOI
PubMed
高影响因子
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