BIOMATERIALS
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2025
·
IF 12.9
Zishan Zeng,Jingwen Jiang,Yue Sun,Wanzhen Li,Dong Zheng,Huanxin Lin,Chunshun Zhao
Helicobacter pylori ( H. pylori ) is considered as the major pathogenic factor related to multiple digestive diseases. However, the efficacy of first-line treatment containing antibiotics gradually declined. It is urgent to develop treatment with antibiotic reduction/abandonment to combat H. pylori . Based on our previous discovery that Cu(DTC) 2 exhibited stronger bactericidal effect than that of disulfiram or diethyldithiocarbamate (DTC), we constructed an antibiotic-free therapeutic strategy composed of DTC prodrug, Cu 2+ and shikonin (SK) to eliminate H. pylori . DTC was firstly modified with nitroaromatic moiety to acquire DTC prodrug (NTR-DTC), which was further encapsulated into Cu-SK@DOPA to construct nanoprodrug Cu-SK@NTR-DTC to achieve the triple masking of DTC, Cu 2+ and SK for the specificity therapeutics. Cu-SK@NTR-DTC could penetrate mucus layer and mainly detain in the bacteria infection area. In the presence of H. pylori , DTC was released from NTR-DTC to recover activity of copper chelation, and competitively bound Cu 2+ from Cu-SK to form Cu(DTC) 2 . The released SK possessed the bactericidal sensitization effect on Cu(DTC) 2 . The H. pylori -activable dissociation of Cu-SK@NTR-DTC, and the local release of Cu(DTC) 2 and SK seriously destructed the bacterial membranes integrity and induce H. pylori death, which provided a feasible strategy to address the clinical limitations of H. pylori clearance.
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JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Xing Li,Jipeng Zhang,Xiangyu Liu,Zijian Wu,Zhipeng Yu,Wen Zhang,Yuanzhi Wang,Zekun Li,Martien A. Cohen Stuart,Leonard M.C. Sagis,Minchun Lv,Jie Xiao,Yuan Li
Helicobacter pylori ( H. pylori ) is a prevalent global pathogen responsible for gastritis and the potential development of gastric cancer. Sulforaphane (SFN), a foodborne compound, exhibits notable antibiotic properties against H. pylori . However, its utility is limited by poor stability and susceptibility to environmental degradation. Here, we developed a gastric-responsive-release microgel for delivering anti- H. pylori SFN. The microgels were prepared by cross-linking α-lactalbumin nanotubes then coated with chitosan (CTS-MGs). SFN was loaded into microgels with a loading rate of 10.73 ± 0.25 %. The CTS-MG showed a strong adhesion to the gastric mucosa, prolonging gastric retention for up to 24 h and responsively releasing SFN in the stomach. Furthermore, CTS-MG/SFN dissociated and released nanotubes/SFN, which could penetrate into the gastric mucus layer and arrive at the deepest mucus sites where most H. pylori were colonized. Our results revealed that CTS-MG/SFN displayed an obvious inhibitory effect against H. pylori . The oral administration of CTS-MG/SFN in H. pylori -infected mice effectively alleviated H. pylori -induced gastritis and modulated gastric microbiota homeostasis. This work demonstrated high potential of CTS-MG microgels for gastric-targeted and oral delivery of antibiotic natural compounds against H. pylori infection.
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ADVANCED FUNCTIONAL MATERIALS
·
2026
·
IF 19.9
Xinqiuyue Wang,Lei Zhang,Jiajia Su,Haokun Xue,Han Zhou,Fanglei Xue,Yajie Wang,Danyi Quan,Jianping Liu,Wenli Zhang
Conventional therapy for Helicobacter pylori ( H. pylori ) is often compromised by host autophagy dysfunction. Host-directed therapy (HDT) presents a viable solution; however, its efficacy is hindered by biological barriers and the difficulty in targeting infected cells. Herein, we developed BPI-CD-L CR , a self-propelled “Trojan Horse” nanoplatform functionalized with bacterial-targeting peptide (B-mBPI) and urease-powered motor (TPGS-β-CD@Urease), in which TPGS-β-cyclodextrin (TPGS-β-CD) plays multiple critical roles from drug delivery to autophagy modulation. Initially, TPGS-β-CD maximizes urease motor activity against the gastric environment by forming a dynamic complex with urease, thereby powering active propulsion for deep mucus penetration. Upon reaching the infection site, BPI-CD-L CR employs a Trojan horse mechanism by tracking bacteria and mediates opsonophagocytosis by macrophages. Meantime, TPGS-β-CD outside facilitates BPI-CD-L CR phagocytosis by increasing the membrane fluidity of infected macrophage via cholesterol extraction. Intracellularly, BPI-CD-L CR modulates the autophagy pathway by promoting autophagosome-lysosome fusion with the aid of TPGS-β-CD and restoring lysosomal function through resveratrol (Res), thereby reactivating the clearance of intracellular bacteria. In the murine infection model, BPI-CD-L CR achieved a remarkable 33-fold reduction in gastric bacterial load compared to antibiotic-based triple therapy. Overall, this platform represents a nanoengineered delivery strategy for intractable infections, providing a promising solution for guiding HDT to achieve on-demand antimicrobial activation within infected cells.
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Advanced Science
·
2026
·
IF 14.1
Yuefan Bai,Hongming Huang,Xudong Hang,Shanwei Hu,Qian Tong,Jingchen Xu,Jia Jia,Hongkai Bi
Helicobacter pylori ( H. pylori ) is a significant global human pathogen intricately linked to gastritis, peptic ulcers, and gastric cancer. The escalating challenge of antimicrobial resistance and the adverse effects of conventional antibiotics on the gut microbiome necessitate the development of novel, targeted therapeutics. In this study, we demonstrate that carnosic acid (CA), a natural compound derived from traditional Chinese medicine, exhibits potent and specific anti- H. pylori activity in vitro, with no detectable resistance observed after prolonged serial passaging. CA also displayed enhanced antibacterial efficacy under physiologically relevant acidic conditions, correlating with its strong inhibition of urease, a key colonization factor for H. pylori . Beyond urease suppression, CA acted through multiple mechanisms, including inhibiting biofilm formation and disrupting mature biofilms, impairing bacterial motility, and compromising cell membrane integrity. In vivo, the combination of CA and omeprazole achieved superior eradication in a mouse model of multidrug-resistant H. pylori infection compared to standard triple therapy. Furthermore, CA treatment showed negligible toxicity to host tissues and minimal disruption to the diversity and composition of the gut microbiota. These findings position CA as a promising lead compound against drug-resistant H. pylori , offering a multi-targeting and microbiota-friendly strategy to combat this pathogen.
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JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Yuanna Shen,Yiqing Zou,Xiaonan Chen,Pengyu Li,Yiqin Rao,Xuan Yang,Yingying Sun,Haiyan Hu
The prevalence of infections with Helicobacter pylori ( H. pylori ) has progressively increased worldwide, which demonstrated to be closely correlated to its biofilm formation. H. pylori biofilms protect the bacteria by significantly decreasing their sensitivity to antibiotics. Moreover, H. pylori colonizes on the gastrointestinal tract epithelium which is covered by mucus layer, acting as another barrier to prevent antibacterial agents from reaching the colonization sites. Herein, we prepared four types of versatile self-assembled nanodrugs (BD/RHL NDs) containing lipophilic alkyl berberine derivatives (BDs) and rhamnolipids (RHL) to overcome the dual obstructions of both mucus layer and biofilms. Molecular dynamics simulations estimated that the driving forces for self-assembly of BD/RHL NDs were electrostatic and hydrophobic interactions. BD/RHL NDs, characterized by appropriate size, negative charge and enhanced hydrophilicity, successfully penetrated through mucus layer without interacting with mucins. In in vitro experiments, BD/RHL NDs exhibited substantial ability to eradicate H. pylori biofilms by destroying their extracellular polymeric substances (EPS) and killing planktonic H. pylori . Furthermore, BD/RHL NDs inhibited the adherence of H. pylori on both biotic and abiotic surfaces, therefore cut off the critical step of the biofilm re-formation which was associated with the recrudescence of infections. In an H. pylori- infected mice model, C10-BD/RHL NDs group showed 40 folds less remnant H. pylori and greater mucosal protection compared with the conventional clinical triple therapy. In conclusion, BD/RHL NDs could penetrate through mucus layer and effectively eradicate H. pylori biofilms in vitro and in vivo , providing a novel strategy for clinical treatment of biofilm-related infections.
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MICROBIAL PATHOGENESIS
·
2023
·
IF 3.8
Zeyuan Huang,Yulin Zhu,Xinhang Li,Zihui Yao,Ruiguang Ge
Helicobacter pylori ( H. pylori ) is a bacterial pathogen in the stomach, causing gastritis , gastric ulcer , duodenal ulcer and even gastric cancer. The triple therapy containing one bismuth-containing compound or a proton-pump inhibitor with two antibiotics was the cornerstone of the treatment of H. pylori infections. However the drug resistance of Helicobacter pylori is more and more common, which leads to the continued decline in the radical cure rate. The purpose of this study was to investigate the mechanism of metronidazole resistance of H . pylori through transcriptomics and biochemical characterizations. In this study, a 128-time-higher metronidazole-resistant H. pylori strain compared to the sensitive strain was domesticated, and 374 significantly differential genes were identified by transcriptomic sequencing as compared to the metronidazole-sensitive strain. Through GO and KEGG enrichment analysis, antibiotic-resistance pathways were found to be mainly involved in redox, biofilm formation and ABC transportation, and the results were verified by qRT-PCR. The subsequent biochemical analysis found that the urease activity of the drug-resistant strain decreased, and whereas the capabilities of bacterial energy production, membrane production and diffusion ability increased. The work here will drop hints for the mechanisms of antibiotic-resistance of H. pylori and provide promising biomarkers for the further development of new-kind drugs to treat metronidazole-resistant H . pylori .
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Nature Communications
·
2017
·Vol. 8
·期 1
·1-12
·
IF 12.124
Li Yunjie,Hu Xiaoxiao,Ding Ding,Zou Yuxiu,Xu Yiting,Wang Xuewei,Zhang Yin,Chen Long,Chen Zhuo,Tan Weihong
Helicobacter pylori infection is implicated in the aetiology of many diseases. Despite numerous studies, a painless, fast and direct method for the in situ detection of H. pylori remains a challenge, mainly due to the strong acidic/enzymatic environment of the gastric mucosa. Herein, we report the use of stable magnetic graphitic nanocapsules (MGNs), for in situ targeted magnetic resonance imaging (MRI) detection of H. pylori . Several layers of graphene as the shell effectively protect the magnetic core from corrosion while retaining the superior contrast effect for MRI in the gastric environment. Boronic-polyethylene glycol molecules were synthesized and modified on the MGN surface for targeted MRI detection. In a mouse model of H. pylori -induced infection, H. pylori was specifically detected through both T 2 -weighted MR imaging and Raman gastric mucosa imaging using functionalized MGNs. These results indicated that enhancement of MRI using MGNs may be a promising diagnostic and bioimaging platform for very harsh conditions.
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CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Jing Wang,Guanghui An,Dongmei Hong,Yinggang Zheng,Hui Zhang,Xinwei Huang,Enduo Feng
Helicobacter pylori ( H. pylori ) infection poses a significant global health burden and is implicated in various chronic gastric diseases. However, current antibiotic therapies are limited by non-specific bacterial targeting, which often results in antimicrobial resistance and disruption of gut microbial homeostasis. To overcome these limitations, we developed a pH-responsive, self-sacrificing cascade nanozyme platform, ZnO 2 -CuNiS@G-Ch, for the targeted eradication of H. pylori . In the highly acidic gastric environment, ZnO 2 rapidly decomposes to release Zn 2+ and H 2 O 2 , initiating selective bacterial killing. Furthermore, the generated H 2 O 2 triggers the cascade activation of CuNiS@G-Ch nanozyme, exhibiting multiple enzyme-like activities-peroxidase (POD), catalase (CAT), and oxidase (OXD) to locally generate reactive oxygen species (ROS) and O 2 , thereby amplifying the bactericidal effect. Notably, upon transiting to the neutral intestinal milieu, the degradation of ZnO 2 was completely suppressed, effectively halting downstream nanozyme activity and preserving the gut microbiota. Comprehensive in vitro and in vivo studies confirmed the robust anti- H. pylori efficacy of ZnO 2 -CuNiS@G-Ch, alongside potent anti-inflammatory effects, gastric mucosal protection, and excellent biocompatibility. This work provides a selective, efficient, and microbiota-friendly strategy for H. pylori therapy, offering a promising alternative to conventional broad-spectrum antibiotics.
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BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Ting-ting Huang,Yan-ni Liu,Jin-Xian Huang,Ping-ping Yan,Jijing Wang,Yong-xiao Cao,Lei Cao
Due to the emergence and spread of multidrug resistance in Helicobacter pylori ( H. pylori ), its eradication has become difficult. Sodium sulfite (SS), a widely used food additive for ensuring food safety and storage, has been recognized as an effective nonbactericidal agent for H. pylori eradication. However, the mechanism by which H. pylori adapts and eventually succumbs under low- or no-oxygen conditions remains unknown. In this study, we aimed to evaluate the anti- H. pylori effect of SS and investigated the multiomics mechanism by which SS kills H. pylori . The results demonstrated that SS effectively eradicated H. pylori both in vitro and in vivo . H. pylori responds to the oxygen changes regulated by SS, downregulates the HcpE gene, which is responsible for redox homeostasis in bacteria, decreases the activities of enzymes related to oxidative stress, and disrupts the outer membrane structure, increasing susceptibility to oxidative stress. Furthermore, SS downregulates the content of cytochrome C in the microaerobic respiratory chain, leading to a sharp decrease in ATP synthesis. Consequently, the accumulation of triglycerides (TGs) in bacteria due to oxidative stress supports anaerobic respiration, meeting their energy requirements. The multifaceted death of H. pylori caused by SS does not result in drug resistance. Thus, screening of the redox homeostasis of HcpE as a new target for H. pylori infection treatment could lead to the development of a novel approach for H. pylori eradication therapy.
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Small
·
2021
·Vol. 17
·期 11
·2006877
·
IF 13.281
Yang Wu,Zhiyong Song,Guiyun Deng,Kai Jiang,Huajuan Wang,Xueji Zhang,Heyou Han
Helicobacter pylori ( H. pylori ) infection has ≈75% probability of causing gastric cancer, so it is considered to be the strongest single risk factor for gastric malignancies. However, the harsh gastric acid environment has created obstacles to medical treatment. This work reports a nanomotor with a bottle-shaped container that can be loaded with small molecules of clarithromycin, nano calcium peroxide (CaO 2 ), and Pt nanoparticles (Pt NPs) by ultrasound. Nanomotors can quickly consume gastric acid through the chemical reaction of CaO 2 to temporarily neutralize gastric acid. The product hydrogen peroxide (H 2 O 2 ) is catalytically decomposed into a large amount of oxygen (O 2 ) by Pt NPs. The local concentration gradient of O 2 bubbles causes it to be expelled from the nanobottles through a narrow opening, and then push the nanobottles forward to provide maximum release and prodrug efficacy. Experiments in animal models show that 15 mg nanomotors can safely and quickly neutralize gastric acid in the stomach and simultaneously release prodrugs to achieve good therapeutic effects without causing acute toxicity. H. pylori burden in mice was 2.6 orders of magnitude lower than that in the control group. The stomach returns to normal pH within 1 d after administration.
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JOURNAL OF CONTROLLED RELEASE
·
2019
·
IF 7.901
Pengyu Li,Xiaonan Chen,Yuanna Shen,Huatian Li,Yiqing Zou,Gang Yuan,Ping Hu,Haiyan Hu
The resistance of Helicobacter pylori ( H. pylori ) to conventional antibiotic treatments becomes prevalent recently. The biofilm formation was found to be highly correlated with the antibiotic resistance of H. pylori in the last decades. Moreover, H. pylori colonizes on the digestive tract epithelium located under the mucus layers, which further reduces therapeutic efficacy as mucus layers trap and remove exogenous substances including drugs. Herein, we reported a novel lipid polymer nanoparticles (LPNs) to overcome both biofilm and mucus layers obstruction. LPNs employed chitosan nanoparticle (CS NPs) as the core, mixed lipid layer containing rhamnolipids (RHL) as the shell and the surface of LPNs was further modified with DSPE-PEG2000 to improve hydrophilicity. Clarithromycin (CLR), a first-line drug for H. pylori infection, was encapsulated in LPNs. LPNs, especially the formulation utilizing 100% of RHL as the lipid shell, exhibited excellent eradicating ability to H. pylori biofilm, which was mainly reflected in the significant reduction of biofilm biomass and viability, destruction of biofilm architecture and elimination of extracellular polymeric substances (EPS). The anti-biofilm activities of LPNs are related to: 1) the disrupting effect of RHL on biofilm matrix; 2) antibacterial effects of CLR and CS NPs on biofilm bacteria and 3) inhibitory effects of CS NPs and RHL on bacteria adhesion and biofilm formation. Furthermore, PEGylated LPNs could rapidly penetrate through mucus without interacting with mucins and effectively eradicate H. pylori biofilm under mucus layer. In conclusion, a novel approach of drug-containing LPNs that could penetrate through mucus layers and effectively eradicate H. pylori biofilm provides new ways to treat persistent H. pylori infections.
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ANALYST
·
2024
·
IF 3.6
Jiaying Wu,Shiyuan Xu,Xuemei Liu,Jingwen Zhao,Zhengfu He,Aiwu Pan,Jianmin Wu
Helicobacter pylori (H. pylori) is a globally widespread bacterial infection. Early diagnosis of this infection is vital for public and individual health. Prevalent diagnosis methods like the isotope 13C or 14C labelled urea breath test (UBT) are not convenient and may do harm to the human body. The use of cross-response gas sensor arrays (GSAs) is an alternative way for label-free detection of metabolite changes in exhaled breath (EB). However, conventional GSAs are complex to prepare, lack reliability, and fail to discriminate subtle changes in EB due to the use of numerous sensing elements and single dimensional signal. This work presents a dual-element multimodal GSA empowered with multimodal sensing signals including conductance (G), capacitance (C), and dissipation factor (DF) to improve the ability for gas recognition and H. pylori-infection diagnosis. Sensitized by poly(diallyldimethylammonium chloride) (PDDA) and the metal–organic framework material NH2-UiO66, the dual-element graphene oxide (GO)-composite GSAs exhibited a high specific surface area and abundant adsorption sites, resulting in high sensitivity, repeatability, and fast response/recovery speed in all three signals. The multimodal sensing signals with rich sensing features allowed the GSA to detect various physicochemical properties of gas analytes, such as charge transfer and polarization ability, enhancing the sensing capabilities for gas discrimination. The dual-element GSA could differentiate different typical standard gases and non-dehumidified EB samples, demonstrating the advantages in EB analysis. In a case–control clinical study on 52 clinical EB samples, the diagnosis model based on the multimodal GSA achieved an accuracy of 94.1%, a sensitivity of 100%, and a specificity of 90.9% for diagnosing H. pylori infection, offering a promising strategy for developing an accurate, non-invasive and label-free method for disease diagnosis.
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