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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

Polysaccharide hydrogel-reinforced nanofibrous composite promotes annulus fibrosus regeneration by regulating mitochondrial antioxidant and metabolic functions

Feng Ling,Xiayu Hu,Yujie Shen,Xi Chen,Zonglai Qian,Hao Liu,Yong Xu,Fan He

Nucleotomy, a surgical procedure employed to address nucleus pulposus (NP) herniation, frequently results in defects within the annulus fibrosus (AF). Owing to the inherently limited self-repair ability of AF tissue, untreated lesions may precipitate reherniation of the NP, thereby accelerating the degeneration of the intervertebral disc. In this study, we introduce a novel composite scaffold comprising hydrogel-reinforced electrospun nanofibers, engineered to mimic the heterogeneous microarchitecture of the native AF matrix while offering improved mechanical support. A mesh-like polycaprolactone (PCL)/gelatin methacryloyl (GelMA) hybrid electrospun nanofibrous membrane was designed to replicate the AF outer region, while a hydrogel mixture of fucoidan methacryloyl (FuMA) and GelMA was sprayed to the membrane surface to emulate the inner region. The integrated FuMA/GelMA hydrogel and PCL/GelMA nanofiber layer enhanced the proliferation of AF cells and markedly improved the synthesis of AF matrix components. Importantly, even under oxidative stress induced by hydrogen peroxide, this hydrogel-reinforced nanofibrous composite effectively maintained the mitochondrial functions of AF cells, thereby supporting their energy metabolism and matrix anabolism. Further molecular experiments unraveled that this composite protected AF cells from oxidative damage through activation of the NRF2-mediated antioxidant enzymes, such as heme oxygenase 1. In a rat caudal disc box defect model, the implantation of a hydrogel-reinforced nanofibrous composite promoted the regeneration of AF tissue, preserved the hydration of NP tissue, and inhibited intervertebral disc degeneration. This approach represents a promising strategy for the repair of nucleotomy-induced AF damage, thereby offering potential therapeutic benefits for patients experiencing intervertebral disc degeneration.

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Discover Nano · 2026 ·Vol. 21 ·期 1 ·415 · IF 6.7

Hesperetin loaded fucoidan selenium nanoparticles alleviate cisplatin induced acute kidney injury via antioxidant and cGAS STING pathway regulation

Long Lin,Zhang Yexi,Xiao Jun,Zang Jianhua

Purpose To fabricate hesperetin-loaded fucoidan-selenium (Hes/Fu-Se) nanoparticles (NPs) for alleviating cisplatin-induced acute kidney injury (AKI), overcoming hesperetin’s low solubility and bioavailability and boosting antioxidant and anti-inflammatory efficacy. Methods Hes/Fu-Se NPs were prepared by encapsulating hesperetin within fucoidan, and then functionalized selenium (Se) NPs. Nanoparticle physicochemical properties and antioxidant activity (FRAP, ABTS) were characterized. Cisplatin-stimulated HK-2 cells were used for in vitro detection of cell viability, apoptosis, ROS accumulation, mitochondrial function and cGAS-STING signaling. A cisplatin-induced AKI mouse model was adopted to test renal biochemical indexes, renal histopathology and renal injury-related protein expression. Results Synthesized Hes/Fu-Se NPs exhibited uniform particle size, superior aqueous solubility and potent antioxidant activity. In vitro, the NPs restored HK-2 cell viability, mitigated apoptosis and ROS overproduction, and inhibited DNA damage and cGAS-STING cascade activation. In vivo, Hes/Fu-Se markedly reduced serum BUN and CRE, alleviated renal histological lesions and inflammatory infiltration, and downregulated the expression of cGAS, STING, γH2AX and TNF-α in kidney tissues. Conclusions Hes/Fu-Se NPs relieve cisplatin-triggered AKI via amplified antioxidation, DNA damage restoration and cGAS-STING pathway suppression. This nanoformulation provides a promising nephroprotective strategy against chemotherapy-related renal toxicity for clinical translation. Graphical abstract

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npj Science of Food · 2026 · IF 9.7

Fucoidan restores age-associated intestinal homeostasis in aged mice

Xie Shufu,McClements David Julian,Hong Qing,Liu Zhenmin,Zhang Zipei,Qiu Chao,Zhao Jianwei,Jin Zhengyu,Chen Long

With global aging, intestinal homeostasis disruption contributes to inflammation, oxidative stress, and metabolic disorders. This study assessed fucoidan at doses of 100, 250 and 500 mg/kg in aged mice. The high dose (500 mg/kg) improved food intake, body weight and intestinal transit, and elevated α-amylase activity. It also relieved oxidative stress, strengthened intestinal tight junctions and restored mucosal morphology. Multi-omics analyses revealed that fucoidan reshaped the gut microbiome—enriching beneficial taxa (e.g., Akkermansia ) while suppressing opportunistic pathogens—and increased short-chain fatty acid production. Untargeted metabolomics indicated enrichment of antioxidant and barrier-protective metabolites and clearance of cytotoxic compounds, with key impacts on amino acid, lipid, and energy metabolism. Overall, fucoidan systematically restores aging intestinal homeostasis via a “microbiota–metabolite–host” axis, supporting its potential as an anti-aging functional food.

CAS / MDL: 9072-19-9
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Innovative Food Science & Emerging Technologies · 2026 · IF 6.9

Glycation regulation between dual-natural milk-derived proteins and fucoidan by dielectric barrier discharge-cold plasma and its potential for delivery of astaxanthin

Yangcheng Ge,Yingcong Yang,Zhen Xu,Gongshuai Song,Mengna Zhang,Jinyan Gong

Milk proteins are attractive building blocks for food-grade delivery systems due to their biocompatibility and versatile functionality. However, their structural instability and limited protection capacity for lipophilic bioactives restrict broader applications. In this study, β-lactoglobulin fibrils (β-LGF) and β-casein (β-CN) were self-assembled to construct a dual-natural milk-protein complex, followed by dielectric barrier discharge cold plasma (DBD-CP)-assisted glycation with fucoidan (FD) to develop a novel protein-polysaccharide conjugate for astaxanthin (AST) delivery. The structural characteristic, physicochemical property, antioxidant activity, and emulsifying performance of the conjugate were systematically investigated. The β-LGF/β-CN complex at a mass ratio of 1:1 exhibited optimal properties, including reduced particle size, enhanced thermal stability, increased apparent viscosity, and the highest DPPH radical scavenging activity (21.05%). CP-assisted glycation significantly increased the degree of glycation from 9.83% to 18.07%, accompanied by the increased β-sheet content, strengthened intermolecular interactions, and formation of high-molecular-weight conjugates. The LGF-CN-FD conjugate showed superior antioxidant capacity and structural stability. AST-loaded emulsions stabilized by the conjugate achieved the highest encapsulation efficiency (80.57%) and loading capacity (10.73%). In vitro digestion demonstrated enhanced gastric protection (63.25% AST retention) and improved bioaccessibility (51.07%). This work demonstrates that CP-assisted glycation effectively tailors the structure and functionality of dual milk-protein assemblies, providing a simple and efficient strategy to design robust colloidal delivery systems for lipophilic bioactives in functional foods.

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Microbiome · 2026 · IF 14.9

Host-driven evolution shapes the polysaccharide utilization profiles of alga-associated Flavobacteriaceae

Guanjing Cai,Yingying Wu,Ziming Chen,Xiaoyu Yang,Xue Jiang,Qingshuang Wang,Runlin Cai,Hui Wang

Background Marine algae represent major producers of complex polysaccharides and serve as hosts for diverse microbial communities in the phycosphere. Flavobacteriaceae are among the key bacterial taxa involved in polysaccharide degradation and carbon remineralization in this environment. However, the extent to which algal hosts drive the divergence of polysaccharide utilization profiles in these bacteria remains unclear. Results We conducted a genome-resolved analysis of 103 cultured Flavobacteriaceae strains isolated from red, green, and brown macroalgae, as well as from diatoms and dinoflagellates. We found that macroalga-associated strains generally harbored more abundant and diverse CAZyme-encoding genes than their microalga-associated counterparts. Moreover, strains associated with different algal phyla showed distinct metabolic specializations that aligned with the typical polysaccharides of their respective hosts, strongly supporting host-specific adaptation. In four widely distributed genera ( Maribacter , Flagellimonas , Polaribacter , Winogradskyella ), CAZyme profile dissimilarity and key glycoside hydrolase gene divergence exhibited phylogenetic congruence with algal host phylogeny (Mantel r up to 0.76 and 0.85, respectively), indicative of host-associated functional adaptation. Using Maribacter as a model, cultivation experiments and transcriptome characterization demonstrated that polysaccharide utilization efficiency is not solely linked to the organization of genes into polysaccharide utilization loci (PULs), but also associated with the expression dynamics of key transcription factors (TFs), particularly those from AraC and DeoR families, whose expression patterns were coordinated with laminarin degradation. Notably, these two TF families also exhibited host-associated divergence patterns similar to those of CAZyme-encoding genes. Furthermore, analysis of the Tara Oceans metagenomic data indicated that, within the AraC and DeoR families, a higher proportion of genes were positively correlated with chlorophyll a content compared to other TF families, reinforcing their specialized roles in alga-associated bacterial lifestyles. Conclusions Our integrative genomic and transcriptomic analyses reveal evolutionary and regulatory adaptation of marine Flavobacteriaceae to distinct algal hosts. These findings highlight algae-derived habitats as specialized niches that shape microbial metabolic potential, and suggest that carbohydrate metabolism plays a key role in host-driven bacterial evolution across global oceans. Your browser is not supporting the HTML5

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International Journal of Pharmaceutics-X · 2025 · IF 6.4

Improved bioavailability and anti-nephrotoxicity efficacy of polydatin on cisplatin-induced AKI via a dual-targeting fucoidan delivery system

Yinghan Wang,Shichao Liu,Feikai Zhu,Xuefei Wang,Hanyu Wang,Lin Long,Jun Xiao,Chuanlong Guo

Acute kidney injury (AKI) is a common and serious complication in clinical practice, especially when using chemotherapy drug cisplatin, which severely limits its anti-cancer efficacy. This study developed a novel nano delivery system (Fu-4-PBA/Po NPs) that combines fucoidan (Fu), endoplasmic reticulum stress (ERS) inhibitor 4-phenylbutyric acid (4-PBA), and natural antioxidant Polydatin (Po) to simultaneously alleviate cisplatin induced oxidative stress and ERS. The optimized Fu-4-PBA/Po NPs showed an average size of 102 ± 3.46 nm, a zeta potential of −16.5 ± 0.49 mV, and a high drug loading capacity of 10.34 ± 0.6 %. They exhibited excellent stability and a sustained release profile in vitro . In vitro results showed that treatment with Fu-4-PBA/Po NPs led to a marked increase in cell survival by 34.73 ± 3.54 percentage points compared to the model group, which had a survival rate of 45.97 ± 2.76 %. Furthermore, Fu-4-PBA/Po NPs effectively inhibited the accumulation of reactive oxygen species (ROS), mitochondrial membrane potential decline, and calcium ion release by targeting P-selectin and endoplasmic reticulum (ER) at the site of inflammation, and significantly alleviate cisplatin induced cell apoptosis. Mechanism studies showed that nanocomposites alleviate ERS by inhibiting the PERK-eIF2α-ATF4-CHOP pathway, while blocking the activation of the cGAS-STING pathway, thereby reducing DNA damage and inflammatory response. Pharmacokinetic studies showed that the peak concentration (Cmax) of the nanoparticles reached 2.2 times that of free Po, and the area under the curve (AUC) increased by 2 times. In animal studies, administration of Fu-4-PBA/Po NPs at a dose of 100 mg/kg notably ameliorated renal function, as indicated by reductions in serum creatinine (SCr) and blood urea nitrogen (BUN) levels by 84.3 % and 62.4 %, respectively, and also improved kidney histopathology. This study provided a dual targeted nano-delivery strategy for cisplatin induced AKI therapy, which has important clinical application potential.

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Journal of Extracellular Vesicles · 2025 ·Vol. 14 ·期 6 ·e70105 · IF 14.5

Macrophages Internalize Epithelial‐Derived Extracellular Vesicles That Contain Ferritin via the Macrophage Scavenger Receptor 1 to Promote Inflammatory Bowel Disease

Wenxin Zhang,Weichen Dong,Chen Cheng,Hongting Zhao,Yutong Liu,Kristina Zaydel,Liora Frech,Zhiyao Xing,Wusheng Zhu,Bing Zhou,Yi Li,Esther G Meyron‐Holtz,Kuanyu Li

The incidence of inflammatory bowel disease (IBD) is on the rise, yet current clinical treatments are limited. Previous studies have identified impairments in both systemic and local iron metabolism in IBD patients. However, the impact of iron dyshomeostasis on the development and pathogenesis of IBD remains elusive. In this study, we confirmed iron deposition in inflamed intestinal lesions of IBD patients and mice with DSS‐induced colitis, accompanied by distinct distribution patterns of the iron storage protein ferritin. To reveal the role of ferritin in the involvement of pathology of IBD, we constructed intestinal epithelial cell‐ or myeloid‐specific ferritin H ( FtH ) knockout mice and demonstrated that intestinal epithelial cells (IECs) release extracellular vesicles (EVs) that contain iron‐loaded ferritin. These EVs are internalized by macrophages via the macrophage scavenger receptor 1 (Msr1), leading to the activation of inflammatory responses and oxidative stress, thereby exacerbating colitis severity. Genetic deletion of FtH in IECs or blockage of macrophage ferritin uptake, either through Msr1 inhibitor fucoidan or through Msr1 knockdown (KD), suppressed inflammatory symptoms. Thus, EVs containing iron‐loaded ferritin released from IECs activate macrophages and contribute to IBD development, supporting that IBD patients with iron deficiency anaemia are often prescribed iron supplementation in a remission phase, other than in an active phase of the disease. Pharmacological inhibition of this ferritin secretion and engulfing process provides a therapeutic target for the disease. This study explores the interaction between intestinal epithelial cells (IECs) and macrophages through extracellular vesicles (EVs) in the context of inflammatory bowel disease (IBD). IECs release iron‐loaded ferritin via EVs as the donor, while macrophage scavenger receptor 1 on the surface of macrophages serves as the receptor for the internalization of the iron‐loaded ferritin‐containing EVs. This process activates macrophages and contributes to the development of IBD. These findings highlight the pathophysiological significance of iron metabolism disorders and suggest potential targets for future clinical applications in patients with IBD.

CAS / MDL: 9072-19-9
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Food Bioscience · 2025 · IF 5.9

Encapsulated black rice anthocyanins by mildly heat-induced egg yolk immunoglobulin and fucoidan with electrostatic interaction to enhance stability and delay the oxidation of yak meat

Xuepeng Li,Fuyao Li,Yu Zeng,Hong Zhang,Xuepeng Lv,Yiwei Tang

This study enhanced the stability of black rice anthocyanins (ANS) by gently inducing the formation of electrostatic encapsulation particles through the synergistic interaction of egg yolk immunoglobulin (IGY) and fucoidan. Results showed that after heat induction at 40 °C, the increasing α-helices content in the protein facilitated its binding with anthocyanins, and effectively improved thermal stability by 20.16 %. Additionally, fucoidan effectively reduced anthocyanin degradation caused by illumination (15.01 %) and vitamin C (46.87 %) by forming of a dense surrounding layer on the complex's surface through electrostatic interactions with IGY, which promoted the aggregation of protein and anthocyanin, while maintaining a high anthocyanin retention rate and total reducing capacity during in vitro digestion. Moreover, the results of yak meat storage demonstrated that the stable complex structure of fucoidan/egg yolk immunoglobulin complex facilitated the slow release of anthocyanins, thereby effectively delaying lipid oxidation during the preservation of yak meat. This study provides a theoretical basis for enhancing the stability of anthocyanins.

CAS / MDL: 9072-19-9
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EUROPEAN POLYMER JOURNAL · 2026 · IF 6.8

Multifunctional hydrogel integrating phototherapy and tumor microenvironment remodeling combined with immunotherapy for synergistic treatment of HCC

Guolong Zhang,Wenjing Feng,Chenying Liu,Linhua Wang,Cui Cheng,Xiao Han,Wenjuan Chen

This study develops a multifunctional hydrogel that achieves highly effective treatment of hepatocellular carcinoma (HCC) by combining phototherapy with immunotherapy and remodeling tumor microenvironment (TME). The hydrogel is prepared via dynamic Schiff base crosslinking between carboxymethyl chitosan and four-arm PEG benzaldehyde, incorporating polyvinylpyrrolidone-modified Bi 2 WO 6-x (BWO-PVP) nanoparticles and fucoidan (Fu). In vitro studies demonstrate that the hydrogel exhibites good self-healing properties, injectability, and TME-responsive degradation behavior. Under 808 nm laser irradiation, it generates substantial hyperthermia and reactive oxygen species, leading to significant inhibition of HepG2 cell proliferation. Moreover, the hydrogel can release Fu to suppresse the activation of cancer-associated fibroblasts (CAFs), which contributing to TME remodeling. In H22 hepatoma-bearing mice, the hydrogel can also load the STING agonist (cyclic dinucleotide, CDN), thereby suppressing tumor growth and reversing immunosuppressive TME conditions. Hence, this combinatory strategy provides a promising platform for enhancing HCC treatment through integrated phototherapy, TME regulation and immunotherapy.

CAS / MDL: 9072-19-9
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ADVANCED FUNCTIONAL MATERIALS · 2026 · IF 19

Preferential Drug Loading into Platelet α Granules Boosts Inflammation-Targeted Delivery in Rheumatoid Arthritis

Jiao Li,Xin Wen,Bin Zhang,Jianheng Ren,Zhumei Liao,Yuanyi Hua,Xiaohong Li,Qin Wang

In rheumatoid arthritis (RA), circulating platelets (PLTs) migrate to the inflamed synovium and interact with inflammation-resident cells, thereby amplifying inflammatory cascades. Moreover, these PLTs become overactivated and rapidly release α-granule contents in response to an inflammatory stimulus. Thus, the preferential incorporation of therapeutics into α granules can facilitate inflammation-homing trafficking and on-demand drug release. Due to the close crosstalk between PLTs and multiple inflammation-resident cells, precise modulation of PLTs dysfunction holds potential to inhibit the pathological cellular interaction and inflammatory cascades. Owing to the high P-selectin expression on both PLT membranes and α granules, we synthesize a P-selectin-targeted and resveratrol (Res)-loaded nanoparticle BFNPs@Res. After intravenous administration, BFNPs@Res selectively bind to circulating PLTs and accumulate in α granules. These BFNPs@Res-incorporated PLTs subsequently migrate to the inflamed synovium and release therapeutic payloads stored in α granules responding to inflammatory stimulus. Meanwhile, after internalization by PLTs, BFNPs@Res effectively suppress pathological PLTs activation and disrupt their crosstalk with inflammatory cells. In arthritic rats, BFNPs@Res attenuate PLT-mediated inflammatory cell recruitment and effectively alleviate RA symptoms. To our knowledge, this is the first report of exploiting the inflammatory homing and stimulus-responsive α granule release of PLTs for inflammation-targeted delivery, providing new insight for RA therapy.

CAS / MDL: 9072-19-9
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Materials Today Bio · 2026 · IF 11

Engineering oral celastrol-polysaccharide supramolecular nanoassemblies across intestinal barriers for the intervention of nonalcoholic steatohepatitis

Liming Yang,Yunfei Zhao,Jianguo Luo,Mengjiao Deng,Fangliang Wang,Gang Zou,Jun Chen,Yunyu He,Xuelan Gan,Yumei Dai,Yuminghang Chen,Chao Yu

The development of effective oral therapies for nonalcoholic steatohepatitis (NASH) remains a critical unmet need in clinical practice. Celastrol (CEL), a potent natural compound, is a promising candidate for NASH due to its lipid-modulating, anti-inflammatory properties, and antioxidative properties. However, its clinical translation is severely hindered by poor oral bioavailability and a narrow therapeutic window stemming from significant toxicity. To overcome these limitations, we present the design and fabrication of novel, carrier-free CEL nanoparticles stabilized through natural polysaccharide self-assembly. This innovative formulation strategy is aimed at substantially enhancing the oral bioavailability of CEL, thereby augmenting its therapeutic efficacy in NASH while mitigating associated adverse effects. In this study, we developed a polysaccharide-CEL supramolecular depot comprising 42 distinct nanoassemblies for oral delivery in NASH, identifying chondroitin sulfate (CS) as the optimal polysaccharide adjuvant. The resulting CS/CNA formulation markedly improved oral absorption, with a 3.12-fold increase in observed systemic exposure based on AUC (0-t) compared with free CEL. Inhibitor-based mechanistic studies suggested that CS/CNA transport across intestinal epithelial cells may involve multiple endocytosis pathways and partial lysosomal escape. In a murine model of NASH, CS/CNA demonstrated potent therapeutic efficacy by modulating hepatic inflammation and reducing lipid accumulation. Critically, the nanoassembly exhibited a favorable safety profile, mitigating the toxicity associated with free CEL. By enhancing therapeutic efficacy while reducing adverse effects, this strategy effectively widens the therapeutic window for celastrol. This work establishes CS/CNA as a promising oral therapeutic candidate and provides a robust platform for advancing the clinical potential of CEL for NASH management.

CAS / MDL: 9072-19-9
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Acta Biomaterialia · 2022 · IF 10.633

Bacteria-propelled microtubular motors for efficient penetration and targeting delivery of thrombolytic agents

Songzhi Xie,Chuanfei Mo,Wenxiong Cao,Shuang Xie,Shang Li,Zhanlin Zhang,Xiaohong Li

Effective thrombolysis is critical to rapidly rebuild blood flow for thrombosis patients. Drug delivery systems have been developed to address inadequate pharmacokinetics of thrombolytic agents, but challenges still remain in the timely removal of blood clots regarding the dense fibrin networks. Herein, rod-shaped tubular micromotors were developed to achieve efficient penetration and thorough destruction of thrombi. By using electrospun fiber fragments as the template, urokinase (uPA)-loaded polydopamine (PDA) microtubes with surface decorated fucoidan ( Fu PDA uPA ) were prepared at the aspect ratio of around 2. One E. coli Nissle 1917 (EcN) was assembled into one microtube to construct a Fu PDA uPA @EcN hybrid micromotor through PDA adhesion and L-aspartate induction. The pharmacokinetic analysis indicates that the encapsulation of uPA into micromotors extends the half-life from 0.4 to 5.6 h and increases the bioavailability over 10 times. EcN-propelled motion elevates adsorption capacities of Fu PDA uPA @EcN for more than four times compared with that of Fu PDA uPA . The fucoidan-mediated targeting causes 2-fold higher thrombolysis capacity in vitro and over 10-fold higher uPA accumulation in thrombi in vivo . In the treatment of venous thrombi at mouse hindlimbs, intravenous administration of Fu PDA uPA @EcN completely removed blood clots with almost full recovery of blood flows and apparently alleviated tail bleeding. It should be noted that Fu PDA uPA @EcN treatment at a reduced uPA dose caused no significant difference in the blood flow rate compared with those of Fu PDA uPA . The synergistic action of fucoidan-induced targeting and EcN-driven motion provides a prerequisite for promoting thrombolytic efficacy and reducing uPA dose and bleeding side effect. Statement of significance The standard treatment to thrombosis patient is intravenous infusion of thrombolytic agents, but the associated bleeding complications and impairment of normal haemostasis greatly offset the therapeutic benefits. Drug delivery systems have been developed to address the limitations of inadequate pharmacokinetics of thrombolytic agents, but challenges still exist in less efficient penetration into dense networks for thorough destruction of thrombi. Up to now only few attempts have been made to construct nano-/micromotors for combating thrombosis and there is no single case that antithrombosis is assisted by bacteria or cells-propelled motors. Herein, bacteria-propelled microtubes were developed to carry urokinase for efficient penetration into blood clots and effective thrombolysis. The synergistic action of bacteria-driven motion and specific ligand-induced targeting holds a promising treatment strategy for life-threatening cardiovascular diseases such as thrombosis and atherosclerosis.

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