ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Jiawen Niu,Fawang Zhang,Chenlu Liu,Kunrong Xie,Yuanxiang Zhang,Jie Zhang,Xijun Wang,Chengchao Song,Boyuan Li,Yuhang Jiang,Tianlong Li,Yufu Wang
Regulating microglia to modulate the inflammatory response in the early stages of spinal cord injury is crucial for neural repair. Commonly used drugs to inhibit inflammation and microglial activity in clinical practice, such as glucocorticoids and immunosuppressants, are associated with potential side effects. Eleutheroside B (EB), a natural plant extract, has been demonstrated an efficient anti-inflammatory action with low toxicity and the ability to promote neural repair and axon regeneration, suggesting its potential role in treating SCI. Recently, magnetically driven microrobots have demonstrated the ability to deliver drugs and provide precise targeting in deep tissues, which may help increase the dose of EB at the injury site. In this study, we design biomimetic magnetically driven microrobots loaded with EB, which offer efficient motion control and drug delivery capabilities. In a mouse SCI model, the magnetic microrobot with macrophage membrane functionalized and EBs (MPE robot) actively target the injured area using rotating magnetic fields in the early stages of injury, modulated the local microglial phenotype to a neuroprotective state, inhibited local inflammation, and promote axon regeneration and neurological recovery. This approach demonstrates that a biomimetic microrobot loaded with EB offers an effective strategy for treating SCI and other central nervous system diseases.
研究领域:
生物医学工程
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神经科学
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机器人学
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药理学
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炎症研究
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纳米技术
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DOI
PubMed
高影响因子
Cell Metabolism
·
2025
·
IF 30.9
Yu-Zhang Wang,Wei-Hai Chen,Zi-Yi Han,Shi-Man Zhang,Ping Ji,Cheng Zhang,Jun-Long Liang,Xian-Zheng Zhang
Bacteria-based metabolic therapy has been acknowledged as a promising strategy for tumor treatment. However, the insufficient efficiency of wild-type bacteria severely restricts their therapeutic efficacy. Here, we elaborately develop an ʟ-cyst(e)ine-addicted bacteria-nanodrug biohybrid for metabolic therapy through a dual-selection directed evolution strategy. Our evolved strain exhibits a 36-fold increase in ʟ-cystine uptake and a 23-fold improvement in total activity of cysteine desulfhydrases compared with the wild-type strain. By conjugating with DMXAA-loaded liposomes, the engineered bacteria-nanodrug biohybrid not only prevents the influx of nutrients into the tumor by blocking neovasculature but also achieves efficient and durable CySS catabolism locally. The unavailable of Cys species disrupts redox homeostasis and strikingly increases intracellular ROS level, achieving favorable therapeutic outcomes in multiple tumor models. Our study not only highlights the promise of directed evolution strategy in enhancing the stability and efficiency of bacteria-based living biocatalyst but also provides new opportunities for antitumor metabolic therapy.
研究领域:
生物医学工程
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肿瘤学
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合成生物学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Yuchen Zhang,Shuang Feng,Jie Luo,Kaige Xu,Junfeng Guo,Xingyue Zhang,Mengxue Yuan,Qiang Luo,Yu Huang,Chaoqiang Fan,Kibret Mequanint,Donghui Zhu,Malcolm Xing,Shiming Yang
The cGAS-STING signaling pathway effectively activates antitumor immune responses and holds promise for overcoming drug resistance in hepatocellular carcinoma (HCC) immunotherapy. However, achieving specific activation of this pathway in HCC remains challenging. Here, it is introduced a single-metal-doped nanoplatform, ZMRPF, which leverages ferroptosis-induced mitochondrial DNA (mtDNA) release to stimulate cGAS-STING-mediated immune activation. ZMRPF initiates HCC ferroptosis by inducing high levels of lipid reactive oxygen species, leading to mitochondrial stress and the release of endogenous mtDNA. This mtDNA synergistically activates the cGAS-STING pathway, enhanced by immunoactivating Mn 2 ⁺ ions released from ZMRPF. Concurrently, the tumor antigens released during ferroptosis amplify the activity of antigen-presenting cells, creating a cascade that links ferroptosis with innate immunity. This cascade drives a robust systemic antitumor immune response, effectively reversing the immunosuppressive microenvironment of HCC. These results demonstrate the ability of ZMRPF to reshape the immune microenvironment of HCC and offer a promising strategy for next-generation tumor immunotherapy.
研究领域:
肿瘤学
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免疫治疗
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纳米医学
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分子生物学
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癌症免疫学
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产品关联
DOI
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Sitong Ma,Jingbo Liu,Yajuan Li,Yingying Liu,Shanglin Li,Yang Liu,Ting Zhang,Meng Yang,Chunmei Liu,Zhiyang Du
Oral co-delivery of nutraceuticals at colon sites has been considered the preferable strategy for targeted ulcerative colitis (UC) relief. This study aimed to develop oral colon-targeting nanoparticles (NPs) co-loaded with egg white-derived peptides (EWDP) and hydrophobic quercetin (Que) using Zein/chondroitin sulfate (CS) templates. The fabricated NPs showed excellent pH-sensitive size tunability (488.0–128.6 nm) and Que co-encapsulation efficiency (99.3%, pH 7.0), owing to the EWDP co-assembly with templates driven by three main noncovalent interactions (hydrogen bonding, electrostatic and hydrophobic interaction). Notably, the less active EWDP could act as the promising co-assembly enhancers and excipient analogs to sufficiently exert the preferable oral synergism (e.g., antioxidant and anti-inflammatory) of the two nutraceuticals, mainly through enhancing its aqueous solubility, controlled release, and transport stability of Que (>20%) under gastrointestinal conditions. Moreover, EWDP could jointly co-assembly with active targeting biopolymers (e.g., CS) to induce the superior colon-targeted accumulation of NPs, thereby dramatically repairing intestinal barriers (tight junction and mucus layer) and restoring gut microbiota balance (e.g., enriching Lachnospiraceae and eliminating Bacteroidota ). Overall, this study provides a facile and efficient orally colon-targeted nano-strategy for multiple nutraceuticals in precise UC mitigation. Meanwhile, the co-assembly profiles of EWDP could offer an insightful and widely applicable insight into the ingenious formulation of biopolymer nanoplatforms (active targeting or passive targeting) in food processing and healthcare areas.
研究领域:
食品科学
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生物医学工程
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药剂学
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DOI
高影响因子
Molecular Medicine Reports
·
2024
·Vol. 30
·期 2
·1-15
·
IF 3.4
Jingxia Du,Yibo Dong,Jingjing Song,Hanqi Shui,Chengyao Xiao,Yue Hu,Shiyao Zhou,Shanshan Wang
Myocardial ischemia/reperfusion injury (MIRI) is a significant challenge in the management of myocardial ischemic disease. Extensive evidence suggests that the macrophage‑mediated inflammatory response may play a vital role in MIRI. Mesenchymal stem cells and, in particular, exosomes derived from these cells, may be key mediators of myocardial injury and repair. However, whether exosomes protect the heart by regulating the polarization of macrophages and the exact mechanisms involved are poorly understood. The present study aimed to determine whether exosomes secreted by bone marrow mesenchymal stem cells (BMSC‑Exo) harboring miR‑25‑3p can alter the phenotype of macrophages by affecting the JAK2/STAT3 signaling pathway, which reduces the inflammatory response and protects against MIRI. An in vivo MIRI model was established in rats by ligating the anterior descending region of the left coronary artery for 30 min followed by reperfusion for 120 min, and BMSC‑Exo carrying miR‑25‑3p (BMSC‑Exo‑25‑3p) were administered through tail vein injection. A hypoxia‑reoxygenation model of H9C2 cells was established, and the cells were cocultured with BMSC‑Exo‑25‑3p in vitro. The results of the present study demonstrated that BMSC‑Exo or BMSC‑Exo‑25‑3p could be taken up by cardiomyocytes in vivo and H9C2 cells in vitro. BMSC‑Exo‑25‑3p demonstrated powerful cardioprotective effects by decreasing the cardiac infarct size, reducing the incidence of malignant arrhythmias and attenuating myocardial enzyme activity, as indicated by lactate dehydrogenase and creatine kinase levels. It induced M1‑like macrophage polarization after myocardial ischemia/reperfusion (I/R), as evidenced by the increase in iNOS expression through immunofluorescence staining and upregulation of proinflammatory cytokines through RT‑qPCR, such as interleukin‑1β (IL‑1β) and interleukin‑6 (IL‑6). As hypothesized, BMSC‑Exo‑25‑3p inhibited M1‑like macrophage polarization and proinflammatory cytokine expression while promoting M2‑like macrophage polarization. Mechanistically, the JAK2/STAT3 signaling pathway was activated after I/R in vivo and in LPS‑stimulated macrophages in vitro, and BMSC‑Exo‑25‑3p pretreatment inhibited this activation. The results of the present study indicate that the attenuation of MIRI by BMSC‑Exo‑25‑3p may be related to JAK2/STAT3 signaling pathway inactivation and subsequent inhibition of M1‑like macrophage polarization.
研究领域:
心脏病学
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分子生物学
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干细胞研究
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炎症
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外泌体治疗
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产品关联
DOI
PubMed
高影响因子
Materials Advances
·
2024
·Vol. 5
·期 6
·2456-2469
·
IF 5.2
Haihua Zhou,Hongyan Pan,Faisal Raza,Hajra Zafar,Yu Ge,Nan Wang,Ronglei Zheng,Degeng Zhang,Yanmin Yang
Cancer is a grave threat to human life and well-being today. Photothermal therapy, a non-invasive method that converts light energy into heat energy to eliminate tumor cells, has emerged as a promising approach. In this study, bismuth nanosheets were utilized as photothermal agents, while 5-fluorouracil and metformin served as model drugs. By designing a temperature-sensitive liposome (BiNSs/Met/5-FU@TSL) that encapsulates bismuth nanosheets, a multifunctional drug delivery system was developed, combining photothermal therapy with synergistic chemotherapy for enhanced anti-tumor effects. Through transmission electron microscopy, it was confirmed that bismuthene nanosheets were successfully encapsulated in stable and uniformly spherical liposomes. Photothermal performance tests demonstrated the system's effectiveness and stability in generating heat. In vitro release experiments further confirmed the thermosensitive liposomes’ responsiveness to photothermal stimuli. Both in vitro and in vivo studies showcased the system's excellent anti-tumor effects and the safety of the blank carriers. This research presents a novel concept, providing insights into the combination of tumor photothermal therapy with chemotherapy, opening new avenues for effective cancer treatment.
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高影响因子
FOOD HYDROCOLLOIDS
·
2024
·
IF 11
Na Yu,Wenbao Zuo,Linyu Ma,Jianhong Yang,Haliza Katas
Dysphagia-affected populations are facing crucial challenges on oral administration of medicines and health products because of swallowing malfunction with a high risk of aspiration. The current countermeasures that relied mainly on modification of existing formulations with thickened liquids comes with potential hazards, e.g., bioavailability alterations and unsatisfactory safety. Thus, dysphagia-specific oral delivery system is in critical need of development. Herein, a swallowing dynamics-inspired, oleogel-in-hydrogel Pickering emulsion fluid gel was proposed as a versatile oral delivery system for patients with dysphagia. With the dual structure of high acyl gellan gum (HAG) fluid gel and whey protein isolate (WPI) stabilized oleogel-in-hydrogel Pickering emulsion gel, the novel system demonstrated the potential to tackle both swallowing and drug encapsulation challenges. Specifically, it displayed good shear flowability during shearing and appropriate extensional capabilities after shearing which are well-matched with swallowing dynamics to facilitate ease and safe swallowing. Moreover, the oleogel-in-hydrogel Pickering emulsion gel structure enables its versatile loading potential for both hydrophilic and lipophilic substances. Remarkably, the microstructure and the related rheological properties of this novel system could be tailored by controlling critical determinants in the formation of fluid gels, namely HAG content and process mixing rate. By adjusting these two parameters, the fluid gels could be customized as preparations with different thickness level for mild, moderate and severe dysphagia, respectively. In conclusion, this proposed approach offers a promising rheologically-tunable oral delivery system for administering bioactives to patients with different levels of dysphagia.
研究领域:
药剂学
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食品科学
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生物医学工程
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DOI
高影响因子
Journal of Translational Medicine
·
2024
·Vol. 22
·期 1
·1-19
·
IF 6.1
Qin Qian,Shan Zhiyan,Xing Lei,Jiang Yutong,Li Mengyue,Fan Linlin,Zeng Xin,Ma Xinrui,Zheng Danyang,Wang Han,Wang Hui,Liu Hao,Liang Shengjun,Wu Lijie,Liang Shuang
Autism spectrum disorder (ASD) is a multifaceted neurodevelopmental disorder predominant in childhood. Despite existing treatments, the benefits are still limited. This study explored the effectiveness of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) loaded with miR-137 in enhancing autism-like behaviors and mitigating neuroinflammation. Utilizing BTBR mice as an autism model, the study demonstrated that intranasal administration of MSC-miR137-EVs ameliorates autism-like behaviors and inhibits pro-inflammatory factors via the TLR4/NF-κB pathway. In vitro evaluation of LPS-activated BV2 cells revealed that MSC-miR137-EVs target the TLR4/NF-κB pathway through miR-137 inhibits proinflammatory M1 microglia. Moreover, bioinformatics analysis identified that MSC-EVs are rich in miR-146a-5p, which targets the TRAF6/NF-κB signaling pathway. In summary, the findings suggest that the integration of MSC-EVs with miR-137 may be a promising therapeutic strategy for ASD, which is worthy of clinical adoption.
研究领域:
神经科学
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干细胞生物学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Meng Yang,Jingbo Liu,Chunmei Liu,Hui Zhang,Shanglin Li,Ting Zhang,Zhipeng Yu,Xiwen Chi,Zhihui Zhang,Zhiyang Du
Orally targeting nanostrategies of multiple nutraceuticals have attracted increasing attention in ulcerative colitis (UC) therapy for superior patient compliance, cost-effectiveness, and biocompatibility. However, the actual targeting delivery and bioefficacy of nutraceuticals are extremely restricted by their poor solubility, interior gastrointestinal retention, and base permeability. Herein, we developed controllable colon-targeting nanoparticles (NPs) composed of a quaternary ammonium chitosan (HTCC) shell and succinic acid-modified γ-cyclodextrin (SACD) core for precise UC treatment. Egg white-derived peptides (EWDP, typical food-derived peptides) could not only function as potential cross-linkers to induce the differential coassembly with the above biopolymers but also aid the hydrophobic curcumin (Cur) solubility as well as nutrition enhancers for oral synergism of colitis therapy. More specifically, NPs with higher EWDP coassembly efficiency exhibited better pH-sensitive colloidal tunability (e.g., smaller size, higher rigidity, and roughness) and robust nutraceuticals (EWDP/Cur) coloading capacity (24.0–33.2% ≫ 10%, pH 2.0–7.0). Compared with pure nutraceuticals, NPs exhibited excellent cellular absorption (almost 10 times) and oral bioavailability (4.19–5.05 times) enhancement via faster mucus permeation and macropinocytosis transport, indirectly regulating the systemic inflammatory response. The sustainable sequential release and targeted accumulation profiles of NPs directly facilitated the interactions with the colonic microenvironment, verified by the intestinal barrier recovery and gut microbiota restoration. Moreover, the critical role of amino acid metabolism reconfirmed the importance of EWDP coassembly efficiency in maintaining intestinal homeostasis. Overall, this study would provide a facile, quantitative, and versatile perspective into the programmable design of food-derived peptide (e.g., EWDP) coassembled nanoplatforms for oral targeted therapy of UC.
研究领域:
生物医药
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纳米医学
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食品科学
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产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Xue Meng,Jianwen Song,Zekun Du,Yongyou Tao,Ji Qi
Pulmonary embolism (PE) is a life-threatening thrombotic condition, yet its precise diagnosis and effective treatment remain a major clinical challenge. In this study, we report the development of a microenvironment-activatable nanoplatform that enables hypoxia-triggered long-wavelength second near-infrared (NIR-II) fluorescence imaging for accurate thrombus visualization, combined with photothermal therapy (PTT) and controlled hydrogen sulfide (H2S) release for synergistic therapeutic intervention. We first synthesize an N-oxide-based molecular probe that undergoes hypoxia-induced structural transition, thereby activating both NIR-II fluorescence and photothermal properties. This probe, together with a thermosensitive H2S donor, is encapsulated into nanoparticles, which are further functionalized with bis-serotonin groups to achieve thrombus-specific targeting via the myeloperoxidase and hydrogen peroxide-mediated aggregation. In a PE mouse model, the nanoagent enables highly selective and sensitive visualization of thrombi via activatable NIR-II fluorescence imaging after intravenous injection, achieving a remarkable signal-to-noise ratio exceeding 120. The combined PTT and H2S therapy significantly enhance thrombolytic efficacy compared to conventional treatment (e.g., urokinase). Importantly, the nanoagent exhibits excellent biocompatibility in vivo, with minimal risk of hemorrhagic complications. This high-performance hypoxia-responsive platform offers a promising strategy for the precise diagnosis and effective treatment of PE and other cardiovascular diseases.
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DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Jingbo Liu,Yang Liu,Shanglin Li,LongJiang Tian,Yajuan Li,Chunmei Liu,Sitong Ma,Ting Zhang,Meng Yang,Zhiyang Du
Efficient oral coassembly strategies have attracted increasing attention for the preferable co-delivery of multiple nutraceuticals. Inspired by superior transport tendencies of the intestinal glucose transporter 2 (GLUT2) to fructose-modified biopolymers, this study fabricated the coassemblies consisting of fructose-modified chitosan (Fru-CS) shell and disulfonic acid-modified γ-cyclodextrin (BA-γ-CD) core to effectively co-deliver hydrophilic egg white oligopeptides (EWOP) and hydrophobic curcumin (Cur). The non-covalent interactions-driven coassemblies exhibited the admirable nanoscale colloidal features and nutraceuticals (EWOP/Cur) co-loading capacity (20.6–25.5 > > 10 %). Besides, the coassemblies introduced the outstanding application synergism (> 15 % enhancement) to nutraceuticals under multi-dimensional scenarios ( e.g. , digestion, heat, UV-light, and antioxidant). Notably, the outer Fru-CS-coated coassemblies could dramatically improve the intact absorption efficiency (2.5–7.9 times) of nutraceuticals mainly via GLUT2-oriented transcytosis and cooperate with BA-γ-CD to achieve better gastrointestinal retention and mucus permeation. This work offers a facile and effective co-assembly strategy for oral co-delivery of nutraceuticals for food processing and healthcare.
研究领域:
食品科学
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营养学
·
生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Ye Zhou,Simeng Wang,Jiahua Guo,Chenghao Li,Mengjun Sui,Zekun Zeng,Hui Dang,Qingqing Gu,Jian Zhu,Yangyang Cheng,Peng Hou
Multimodal treatment of cancer is an unstoppable revolution in clinical application. However, designing a platform that integrates therapeutic modalities with different pharmacokinetic characteristics remains a great challenge. Herein, we designed a universal lipid nanoplatform equipping a ROS-cleavable docetaxel prodrug (DTX-L-DTX) and an NF-E2-related factor 2 (NRF2) inhibitor (clobetasol propionate, CP). This simply fabricated nanomedicine enables superior synergistic molecularly targeted/chemo/radio therapy for lung cancer cascade by a transcription factor-driven ROS self-sustainable motion. Chemotherapy is launched via ROS-triggered DTX release. Subsequently, CP inhibits the expression of NRF2 target genes, resulting in efficient targeted therapy, meanwhile inducing sustained ROS generation which in turn facilitates chemotherapy by overcoming ROS consumption during the DTX release process. Finally, the introduction of radiotherapy further amplifies ROS, offering continuous mutual feedback to amplify the ultimate treatment performance. This strategy is conceptually and operationally simple, providing solutions to challenges in clinical cancer treatment and beyond.
研究领域:
肿瘤学
·
药学
·
生物医学工程
·
分子生物学
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产品关联
DOI
PubMed
高影响因子