Nature Communications
·
2025
·Vol. 16
·期 1
·1-22
·
IF 15.7
Feng Ye,Gao Chao,Peng Xiuyun,Chen Bin,Ding Miaomiao,Du Dailing,Rong Jinghui,Lv Qi,Wilson Daniela A.,Tu Yingfeng,Peng Fei
Hepatic fibrosis involves hepatocyte damage, causing blood ammonia accumulation, which exacerbates liver pathology and crosses the blood-brain barrier, inducing hepatic encephalopathy. It is meaningful to construct a therapeutic platform for targeted ammonia clearance. In this work, a biocompatible water-powered Zn micromotor is constructed as an ammonia chemotaxis platform, which can be actuated by the water splitting reaction and the self-generated Zn 2+ gradient. It can propel towards NH 3 ·H 2 O source through the formation of complex ions [Zn(NH 3 ) 1 ](OH) + and [Zn(NH 3 ) 2 ](OH) + , representing a generalizable chemotaxis strategy via coordination reaction. In vivo, biomimetic collective behavior allows precise navigation and reduction of the intrahepatic ammonia level, reshaping the pathological microenvironment. This mechanism, operating in a green, zero-waste manner, facilitates integration of these micromotors into the domain of biological regulation. Such environment environment-adaptive platform is favorable for targeted treatment of hepatic fibrosis and hepatic encephalopathy caused by hyperammonemia, which is expected to provide inspiration for future personalized and precision medicine.
研究领域:
生物医学工程
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肝脏病学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
PHYSICAL BIOLOGY
·
2022
·Vol. 19
·期 4
·046004
·
IF 2.959
Yue Yang,Caijuan Yue,Chi Zhang,Junhua Yuan
Polymers are important components of the complex fluid environment for microorganisms. The mechanical effects on bacterial motile behavior due to the viscous or viscoelastic properties of polymers were extensively studied, whereas possible chemical effects on bacterial motility through bacterial chemoreception of the polymers were unclear. Here we studied the chemotactic response of Escherichia coli to polymeric solutions by combining the bead assay and FRET measurements. We found that the wild-type E. coli strain exhibited an attractant response to widely used polymers such as Ficoll 400, polyethylene glycol (PEG) 20000 and polyvinyl pyrrolidone (PVP) 360000, and the response amplitude from chemoreception was much larger than that from the load-dependence of motor switching due to viscosity change. The chemotactic response depended on the type of receptors and the chain length of the polymers. Our findings here provided important new ingredients for further studies of bacterial motile behavior in complex fluids.
研究领域:
微生物学
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生物物理学
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产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Qingliang Yang,Xuhui Zhou,Bang Lou,Ning Zheng,Jiale Chen,Gensheng Yang
Despite the booming progress of anticancer nanomedicines in the past two decades, precise tumor-targetability and sufficient tumor-accumulation are less successful and still require further research. To tackle this challenge, herein we present a biomolecular motor (F O F 1 -ATPase)-embedded chromatophore as nanorobot to efficiently overcome biological barriers, and thoroughly investigate its chemotactic motility, tumor-accumulation ability and endocytosis. Chromatophores embedded with F O F 1 -ATPase motors were firstly extracted from Thermus thermophilus, then their properties were fully characterized. Specifically, two microfluidic platforms (laminar flow microchip and tumor microenvironment (TME) microchip) were designed and developed to fully investigate the motility, tumor-accumulation ability and endocytosis of the chromatophore nanorobot (CN). The results from the laminar flow microchip indicated that the obtained CN possessed the strongly positive chemotaxis towards protons. And the TME microchip experiments verified that the CN had a desirable tumor-accumulation ability. Cellular uptake experiments demonstrated that the CN efficiently promoted the endocytosis of the fluorescence DiO into the HT-29 cells. And the in vivo studies revealed that the intravenously administered CN exhibited vigorous tumor-targetability and accumulation ability as well as highly efficient antitumor efficacy. All the results suggested that F O F 1 -ATPase motors-embedded CN could be promising nanomachines with powerful self-propulsion for overcoming physiological barriers and tumor-targeted drug delivery. Statement of significance In this study, we demonstrated that F O F 1 -ATPase-embedded chromatophore nanorobots exhibit a strong proton chemotaxis, which not only plays a key role in tumor-targetability and accumulation, but also promotes tumor tissue penetration and internalization. The results of in vitro and in vivo studies indicated that drug-loaded chromatophore nanorobots are capable to simultaneously accomplish tumor-targeting, accumulation, penetration and internalization for enhanced tumor therapy. Our study provides a fundamental basis for further study on F O F 1 -ATPase-embedded chromatophore as tumor-targeting drug delivery systems that have promising clinical applications. It offers a new and more efficient delivery vehicle for cancer related therapeutics.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
Nano Today
·
2022
·
IF 18.962
Zhentao Zhang,Haiqing Zhong,Yi Zhou,Peng Ke,Qi Dai,Yiying Lu,Xincheng Zhong,Qiyao Yang,Yiyi Xia,Xiaoyan Bao,Linjie Wu,Min Han,Jianqing Gao
The deep penetration in response to specific intratumoral conditions holds considerable potential in achieving a more effective therapy. Lactate is mainly produced by exuberant-metabolism tumor cells growing in the deep center of solid tumor, which would form the characteristic of higher-level lactate deep inside tumor in distance with blood vessels. Herein, inspired by the in vitro directional chemotaxis of enzyme-powered nanomotor driven by substrate gradient, a novel lactate oxidase (LOX)-powered Pt Nanoflowers (Pt NFs) was developed to achieve deep intratumoral penetration triggered by the lactate-driving positive chemotaxis that was confirmed both in vitro and in vivo for the first time. Besides, LOX-powered Pt NFs with self-oxygenation could achieve a more thorough effect on hypoxic relief via the cascading catalysis: (1) the orthotopic extra H 2 O 2 production from lactate catalyzed by LOX, and (2) the effective conversion of both extra-supplement and endogenous H 2 O 2 into O 2 catalyzed by Pt NFs, further overcoming the hypoxia-induced radioresistance . Meanwhile, the X-ray radiation deposited inside Pt NFs could improve low-dose radiotherapy effect with increasing ROS level and enhancing nuclear DNA damage. Collectively, this work would provide a blueprint for developing substrate gradient-driving "smart" delivery systems and radiosensitization strategy.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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产品关联
DOI
高影响因子
Nanomaterials
·
2022
·Vol. 12
·期 12
·2049
·
IF 5.719
Tianyu Gao,Jinwei Lin,Leilei Xu,Jianguo Guan
In living bodies, pH values, which are precisely regulated and closely associated with diseased cells, can act as an efficient biologically intrinsic indicator for future intelligent biomedicine microsystems. In this work, we have developed flask-like carbonaceous nanomotors (FCNMs), via loading Fe3O4nanoparticles (NPs) into a cavity, which exhibit a self-adaptive feature to a specific physiological pH by virtue of the pH-dependent dual enzyme-like activities of Fe3O4NPs. Specifically, the peroxidase-like activity of Fe3O4NPs in an acidic pH range, and the catalase-like activity in a near neutral and alkaline pH range, determine the products in the motion system (•OH, ions and O2), whose diffusions from the inner to the outside of the flask result in fluid movement providing the driving force for the movement of the FCNMs. Correspondingly, changes of the product concentrations and species in the physiological pH range (4.4–7.4) result, firstly, in velocity decrease and, then, with increase in pH, increase of the FCNMs occurs. Thanks to the non-linear velocity responsiveness, the FCNMs show intriguing pH taxis towards 6.8 (generally corresponding to the physiological pH in tumor microenvironments), where a maximum velocity appears. Furthermore, the superparamagnetic feature of the Fe3O4NPs simultaneously endows the FCNMs with the abilities to be magnetic-oriented and easily separated. This work could significantly increase the possibility of nanomotors for targeted therapy of tumors and next-generation biotechnological applications.Keywords:nanomotors;pH responsiveness;Fe3O4nanoparticles;dual enzyme-like activities;physiological pH chemotaxis
研究领域:
生物医学工程
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纳米医学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Minxia Zhu,Luwen Zhu,Yuchan You,Mingchen Sun,Feiyang Jin,Yanling Song,Jucong Zhang,Xiaoling Xu,Jiansong Ji,Yongzhong Du
Tumor interstitial pressure represents the greatest barrier against drug diffusion into the depth of the tumor. Biometric nanomotors highlight the possibility of enhanced deep penetration and improve cellular uptake. However, control of their directionality remains difficult to achieve. Herein, we report cysteine-arginine-glutamic acid-lysine-alanine (CREKA)-modified ceria@polydopamine nanobowls as tumor microenvironment-fueled nanoscale motors for positive chemotaxis into the tumor depth or toward tumor cells. Upon laser irradiation, this nanoswimmer rapidly depletes the tumor microenvironment-specific hydrogen peroxide (H2O2) in the nanobowl, contributing to a self-generated gradient and subsequently propulsion (9.5 μm/s at 46 °C). Moreover, the asymmetrical modification of CREKA on nanobowls could automatically reconfigure the motion direction toward tumor depth or tumor cells in response to receptor–ligand interaction, leading to a deep penetration (70 μm in multicellular spheroids) and enhanced antitumor effects over conventional nanomedicine-induced chemo-photothermal therapy (tumor growth inhibition rate: 84.2% versus 56.9%). Thus, controlling the direction of nanomotors holds considerable potential for improved antitumor responses, especially in solid tumors with high tumor interstitial pressure.
研究领域:
生物医学工程
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Danjun Wu,Kaili Fu,Wangyang Zhang,Yazhen Li,Yaning Ji,Yiwei Dai,Gensheng Yang
The clinical application of 7-ethyl hydroxy-camptothecin (SN-38) maintains challenges not only due to its poor solubility and stability but also the lack of effective carriers to actively deliver SN-38 to deep tumor sites. Although SN-38-based nanomedicines could improve the solubility and stability from different aspects, the tumor targeting efficiency remains very low. Leveraging the hypoxic taxis of bifidobacteria bifidum ( B. bifi ) to the deep tumor area, we report SN-38-based nanomedicines-engineered bifidobacterial complexes for effective tumor-targeted delivery. Firstly, SN-38 was covalently coupled with poly-L-glutamic acid (L-PGA) and obtained soluble polymeric prodrug L-PGA-SN38 to improve its solubility and stability. To prolong the drug release, L-PGA-SN38 was mildly complexed with chitosan to form nanomedicines, and nanomedicines engineered B. bifi were further elaborated via electrostatic interaction of the excess of cationic chitosan shell from nanomedicines and anionic teichoic acid from B. bifi . The engineered B. bifi complexes inherited the bioactivity of native B. bifi and exhibited distinctly enhanced accumulation at the tumor site. More importantly, significantly elevated anti-tumor efficacy was achieved after the treatment of CS-L-PGA-SN38 NPs/ B. bifi complexes, with favorable tumor suppression up to 80%. Such a B. bifi -mediated delivery system offers a promising platform for effective drug delivery and enhanced drug accumulation in the hypoxia deep tumor with superior anti-tumor efficacy.
研究领域:
药学
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生物技术
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肿瘤学
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纳米技术
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产品关联
DOI
PubMed
高影响因子
Frontiers in Plant Science
·
2020
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IF 4.402
Zhang He,Yang Yuxin,Mei Xinyue,Li Ying,Wu Jiaqing,Li Yiwen,Wang Huiling,Huang Huichuan,Yang Min,He Xiahong,Zhu Shusheng,Liu Yixiang
Interspecies interactions play a key role in soil-borne disease suppression in intercropping systems. However, there are limited data on the underlying mechanisms of soil-borne Phytophthora disease suppression. Here, a field experiment confirmed the effects of maize and soybean intercropping on Phytophthora blight of soybean caused by Phytophthora sojae. Experimentally, the roots and root exudates of maize were found to attract P. sojae zoospores and inhibit their motility and the germination of cystospores. Furthermore, five phenolic acids (p-coumaric acid, cinnamic acid, p-hydroxybenzoic acid, vanillic acid, and ferulic acid) that were consistently identified in the root exudates and rhizosphere soil of maize were found to interfere with the infection behavior of P. sojae. Among them, cinnamic acid was associated with significant chemotaxis in zoospores, and p-coumaric acid and cinnamic acid showed strong antimicrobial activity against P. sojae. However, in the rhizosphere soil of soybean, only p-hydroxybenzoic acid, low concentrations of vanillic acid, and ferulic acid were identified. Importantly, the coexistence of five phenolic acids in the maize rhizosphere compared with three phenolic acids in the soybean rhizosphere showed strong synergistic antimicrobial activity against the infection behavior of P. sojae. In summary, the types and concentrations of phenolic acids in maize and soybean rhizosphere soils were found to be crucial factors for Phytophthora disease suppression in this intercropping system.
研究领域:
农业
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植物病理学
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土壤学
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真菌学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Ling Xiao,Yicheng Guo,Fan Wang,Ying Wang,Xisheng Xu,Wenqiang Ni,Bingyun Li,Malcolm Xing,Gaoxing Luo,Rixing Zhan
Although antibiotics have saved many lives, the misuse and overuse of antibiotics have made infectious wound difficult to treat. The antibiotic-free therapy has obtained intense interests. Here we reported that a smart nanohybrid can spontaneously hunt Pseudomonas aeruginosa, a leading opportunistic pathogen causing multi-drug resistance, and then kill them. The nanohybrid is composed of l -lysine conjugated antimicrobial peptide HHC-36 on mussel-inspired coating (PDA) to graphene oxide (GO), namely, l -Lys/ [email protected] We verified, compared and optimized multiple chemoattractants by moving agar plate and quantitative capillary method, and found that l -lysine showed strongest chemotactic effect. Capillary quantitative chemotactic method proves the bacterial chemotactic amount of l -Lys/ [email protected] for 30 min was significant; it can eradicate the captured bacteria using photothermal therapy via NIR. In vivo we found that the bacteria on the wound and within the tissue can be captured and completely eliminated. Due to the outcome of antibacterial activities, l -Lys/ [email protected] showed anti-inflammatory, promoted cell proliferation and vascularization effects in wound healing. This new antibiotic-free nanohybrid to hunt the bacteria, which is promising to avoid tissue damage while killing bacteria and no drug residues in the tissue.
研究领域:
纳米技术
·
生物医学工程
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微生物学
·
伤口愈合
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产品关联
DOI
高影响因子
JOURNAL OF IMMUNOLOGY
·
2024
·
IF 3.6
Gao Along,Lin Yuhua,Chai Yiwen,Han Jugan,Wu Liting,Ye Jianmin
Chemokines play crucial roles in the regulation of immune cell migration and development. The CXCL12/CXCR4 axis has been extensively studied in mammals, but its regulatory mechanism in teleost fish remains unclear. In this study, we used Nile tilapia (Oreochromis niloticus) as a teleost model to investigate the mediation of the CXCL12/CXCR4 axis in IgM+ B cells. Our findings demonstrate that the CXCL12/CXCR4 axis exhibits chemotactic activity on IgM+ B cells and promotes the phagocytosis of IgM+ B cells. Blocking CXCR4 severely impairs the chemotaxis and phagocytosis of IgM+ B cells in vitro and reduces the percentages and numbers of IgM+ B cells that migrate to peripheral blood after pathogen infection in vivo. This reduction in migration leads to a decrease in the inflammatory response, an increase in tissue bacterial load, and a decrease in survival rate. We also discovered that the evolutionarily conserved PI3K-AKT signaling pathway and Girdin are involved in the immune response during Streptococcus agalactiae infection. Inhibitors of the PI3K-AKT signaling pathway prevent the chemotaxis and phagocytosis of IgM+ B cells, impair the expression and phosphorylation levels of related proteins in vitro, and prevent IgM+ B cells chemotaxis into the peripheral blood after pathogen infection in vivo. Furthermore, CXCR4 blocking significantly downregulates the expression of AKT and Girdin. Overall, our study reveals the regulatory mechanism of the CXCL12/CXCR4 axis on IgM+ B cells via the PI3K-AKT signaling pathway in tilapia, suggesting that the functions of the CXCL12/CXCR4 axis in B cells may be conserved between mammals and teleost fish.
研究领域:
免疫学
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分子生物学
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鱼类生理学
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病理生物学
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产品关联
DOI
PubMed
高影响因子
Science Advances
·
2024
·Vol. 10
·期 40
·
IF 11.7
Lian Cui,You Wu,Zeyu Chen,Bingjie Li,Jiangluyi Cai,Zhanhe Chang,Weide Xiao,Yuanyuan Wang,Nan Yang,Yu Wang,Zengyang Yu,Lingling Yao,Rui Ma,Xin Wang,Youdong Chen,Qianyu Chen,Hao Mei,Zhiyi Lan,Yingyuan Yu,Rongfen Chen,Xingbiao Wu,Qian Yu,Jiajing Lu,Ning Yu,Xilin Zhang,Jun Liu,Lingjuan Zhang,Yuping Lai,Shaorong Gao,Yawei Gao,Chunyuan Guo,Yuling Shi
Disrupted N6-methyladenosine (m6A) modification modulates various inflammatory disorders. However, the role of m6A in regulating cutaneous inflammation remains elusive. Here, we reveal that the m6A and its methyltransferase METTL3 are down-regulated in keratinocytes in inflammatory skin diseases. Inducible deletion of Mettl3 in murine keratinocytes results in spontaneous skin inflammation and increases susceptibility to cutaneous inflammation with activation of neutrophil recruitment. Therapeutically, restoration of m6A alleviates the disease phenotypes in mice and suppresses inflammation in human biopsy specimens. We support a model in which m6A modification stabilizes the mRNA of the lipid-metabolizing enzyme ELOVL6 via the m6A reader IGF2BP3, leading to a rewiring of fatty acid metabolism with a reduction in palmitic acid accumulation and, consequently, suppressing neutrophil chemotaxis in cutaneous inflammation. Our findings highlight a previously unrecognized epithelial-intrinsic m6A modification–lipid metabolism pathway that is essential for maintaining epidermal and immune homeostasis and lay the basis for potential therapeutic targeting of m6A modulators to attenuate inflammatory skin diseases.
研究领域:
免疫学
·
分子生物学
·
皮肤病学
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DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Huiyi Liang,Yibo Du,Chenxu Zhu,Zhaoqiang Zhang,Guiqing Liao,Lixin Liu,Yongming Chen
Cancer metastasis that is resistant to conventional therapies has become a major cause of patient death. Recent reports indicate that the neutrophil extracellular trap (NET) is closely associated with cancer distant metastases, and the cell-free DNA of NETs has been identified as the ligand of the transmembrane protein CCDC25 of cancer cells, acting as a chemokine to induce cancer cell migration to distant organs. In this work, we present the poly(aspartic acid) based-cationic materials to interfere with the interaction between NET-DNA and CCDC25, and furthermore to inhibit NET-DNA-mediated cancer cell chemotaxis and migration. Because of a stronger binding affinity to DNA and favorable retention in the liver, nanoparticulate poly(aspartic acid) derivatives (cANP) efficiently reduce the level of hepatic NET-DNA infiltration, leading to a significant suppression of cancer metastases in mice and several human metastatic models. Moreover, the cANP exhibits no toxicity to organs of animals during the entire treatment. Thus, this work suggests a strategy for controlling cancer metastases, which will benefit patients in clinics.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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