bims-engexo 2026-04-12 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–04–12
thirteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Intelligent delivery of autophagy-targeting chimeric peptides by engineered exosomes for the degradation of a-synuclein.
Advances in engineered exosome-loaded hydrogels for bone and cartilage regeneration.
Engineering exosomes with iRGD for targeted RNAi therapy against pancreatic cancer mediated by long non-coding RNA PLBD1-AS1.
Humanized extracellular vesicles for efficient RNA delivery.
Co-Delivery of Ferrostatin-1 and M2 Macrophage-Derived Exosomal Signals via Engineered Hybrid Nanovesicles Enables Synergistic Neuroprotection in Traumatic Brain Injury.
Regenerative effects of myogenic gene transfected MSC derived exosomes on radiation esophagitis.
Delivery of Engineered BMP2 circRNA via Biomimetic Nanovesicles Enhances Titanium Implant Osseointegration Through Translation-Controlled Osteogenesis.
Engineered small extracellular vesicles as bioactive materials: Integrating engineering strategies for cargo loading and targeted delivery systems.
Oral milk-derived exosomes loaded with tafatinib for anti-inflammatory therapy.
NUFIP1-engineered exosomes modulate propofol-induced neurotoxicity in neonatal rats via the ERS apoptotic pathway.
Exosome-Mitochondrial Hybrid Membrane with Targeted Delivery of CO Prevents Mitochondrial Dysfunction and Pyroptosis against Myocardial Ischemia-Reperfusion Injury.
Engineering the Future: Strategic Advances in Extracellular Vesicle-Mediated Drug Delivery Systems.
Orally engineered liver-targeted garlic exosome-like nanovesicles for astaxanthin precise delivery against alcoholic liver disease in mice.

Acta Biomater. 2026 Apr 04. pii: S1742-7061(26)00209-6. [Epub ahead of print]

Intelligent delivery of autophagy-targeting chimeric peptides by engineered exosomes for the degradation of a-synuclein.

Yuteng Zeng, Ziyan Lv, Jiayu Liang, Yetao Wu, Liang Han.

  Targeted degradation of the aggregated α-synuclein holds tremendous potential for treating Parkinson's disease (PD). However, most of the developed aggregated α-synuclein-specific degraders, e.g., autophagy-targeting chimeric peptides, are limited by the blood-brain barrier (BBB), substantia nigra (SN) neuron targetability, and intracytoplasmic release. To overcome these obstacles, we constructed an engineered exosome (EXO) equipped with surficial glucose-regulated protein 94 (GRP94)-targeting peptide N, luminal α-synuclein-degrading peptide P1, and cathepsin-B-cleavable GFLG as the linker between the exosome skeleton protein and P1, termed NEXOGFLG-P1. We verified that the NEXOGFLG-P1 exosomes could cross the BBB and target diseased SN neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced PD model mice. Following fusion with endosomes, the exposed P1 was released into the cytoplasm by cytoplasmic cathepsin B-mediated GFLG cleavage to degrade α-synuclein. Collectively, the NEXOGFLG-P1 exosomes exhibit a significant degradation effect on α-synuclein aggregates, providing a proof-of-concept platform for treating PD. STATEMENT OF SIGNIFICANCE: Targeted degradation of α-synuclein aggregates holds tremendous potential for the etiological treatment of Parkinson's disease (PD). However, most of current α-synuclein-specific degraders are stuck with low blood-brain barrier permeability, poor targetability for diseased cells, and uncontrolled release. Notably, α-synuclein predominantly affects neurons in the substantia nigra (SN) region rather than the whole brain. To overcome these obstacles, we constructed an engineered exosome, termed NEXOGFLG-P1, to specially deliver and release autophagy-targeting chimeric peptide to degrade α-synuclein in the diseased SN neurons through the autophagy-lysosomal pathway. The engineered exosomes exhibit the great potential in targeting diseased SN neurons and degrading α-synuclein aggregates, providing a proof-of-concept therapeutic platform for treating PD.

Keywords:  Engineered exosomes; Parkinson's disease; protein degradation; α-synuclein aggregates

DOI:  https://doi.org/10.1016/j.actbio.2026.04.003
Nanomedicine. 2026 Apr 04. pii: S1549-9634(26)00040-7. [Epub ahead of print] 102939

Advances in engineered exosome-loaded hydrogels for bone and cartilage regeneration.

Meenaloshini Gopalakrishnan, Nandhini Jayaprakash.

  Exosome-loaded hydrogels have emerged as a promising strategy for bone and cartilage regeneration by combining the bioactive signaling of exosomes with the structural support of hydrogels. Exosomes, nanosized extracellular vesicles, mediate intercellular communication by delivering proteins, nucleic acids, and lipids. Incorporation into hydrogels protects exosomes from rapid degradation and enables sustained, localized release at defect sites. Hydrogels provide a biocompatible, extracellular matrix-mimicking environment with tunable physical properties that support tissue repair. Recent advances include affinity-based and stimuli-responsive hydrogels, as well as 3D-printed scaffolds for osteochondral applications. Preclinical studies demonstrate superior regenerative outcomes compared to exosome- or hydrogel-only systems. However, challenges such as exosome heterogeneity, scalability, and regulatory barriers remain. Continued innovations in exosome engineering and smart biomaterials are expected to accelerate clinical translation.

Keywords:  Bone regeneration; Cartilage regeneration; Exosomes; Hydrogels; Tissue engineering

DOI:  https://doi.org/10.1016/j.nano.2026.102939
PLoS One. 2026 ;21(4): e0345697

Engineering exosomes with iRGD for targeted RNAi therapy against pancreatic cancer mediated by long non-coding RNA PLBD1-AS1.

Wenbo Zhu, Xintong Zhao, Weina Hao, Xianzhu Zhou, Congjia Ma, Jiayu Chen, Yating Zhao, Xiangyu Kong, Yiqi Du, Lei Li.

Tumor-derived exosomes play critical roles in pancreatic ductal adenocarcinoma (PDAC) progression by mediating intercellular communication within the tumor microenvironment. This study identifies the long non-coding RNA PLBD1-AS1 as a functional oncogenic lncRNA enriched in PDAC exosomes. We demonstrate that PLBD1-AS1 promotes tumor cell proliferation, migration, and invasion by interacting with the glycolytic enzyme ALDOA and enhancing glycolytic flux. Furthermore, tumor exosomes deliver PLBD1-AS1 to pancreatic stellate cells (PSC), augmenting their glycolysis and facilitating their activation into cancer-associated fibroblasts, thereby shaping a pro-tumorigenic microenvironment. To target it, we developed an engineered exosome system modified with the tumor-penetrating peptide iRGD for specific delivery of siPLBD1-AS1 to both tumor and stromal cells. The resulting iRGD-exo-siPLBD1-AS1 construct demonstrated enhanced cellular uptake and effectively suppressed PLBD1-AS1 expression, inhibited glycolysis, impaired PSC activation, and significantly attenuated tumor growth. Our findings reveal a novel mechanism of exosome-mediated metabolic crosstalk in PDAC and establish a promising RNAi-based therapeutic strategy targeting this lethal malignancy.

DOI: https://doi.org/10.1371/journal.pone.0345697
Proc Natl Acad Sci U S A. 2026 Apr 14. 123(15): e2525726123

Humanized extracellular vesicles for efficient RNA delivery.

Xiang Ma, Sophia R Zhao, Constance L Cepko.

  Engineered extracellular vesicles (EVs) are a class of nonviral delivery vectors for RNA-based vaccines and gene therapies. A specialized form of engineered EVs, known as enveloped protein nanocages (EPNs), has been developed to enhance cargo loading and delivery. When EPNs are equipped with a viral fusogen, such as vesicular stomatitis virus glycoprotein (VSV-G), they have been shown to deliver proteins or RNA efficiently into recipient cells. Comparisons across different EPN types and optimization of their different features have been difficult, as assays for their activity have not been reported for single, active units. As we were interested in optimizing EVs, we first developed a biological titration assay inspired by the methods used for infectious viral particles. With this assay, we optimized EVs using a modular platform, creating EVs composed predominantly of human-derived protein components. This system achieved efficient RNA delivery, with functional titers comparable to those of lentiviral vectors. The optimized chimeric proteins comprising the EV particles integrate domains from human epsin 1, human citramalyl-CoA lyase beta-like protein (CLYBL), and human CEP55. The constructs also include a short 21-amino-acid peptide from a nonhuman source for RNA packaging, resulting in an EV-based RNA delivery system with reduced immunogenicity compared with EPNs and retroviral virus-like particles (VLPs).

Keywords:  EABR; Epsin N-terminal homology (ENTH); citramalyl-CoA lyase beta-like protein (CLYBL); enveloped protein nanocages (EPNs); functional titers

DOI:  https://doi.org/10.1073/pnas.2525726123
ACS Appl Mater Interfaces. 2026 Apr 07.

Co-Delivery of Ferrostatin-1 and M2 Macrophage-Derived Exosomal Signals via Engineered Hybrid Nanovesicles Enables Synergistic Neuroprotection in Traumatic Brain Injury.

Wenyan Hao, Nan Sun, Ruifen Xue, Junkai Chang, Xiaocong Pang, Ying Zhou, Chunsheng Gao.

  Secondary brain injury after traumatic brain injury (TBI) is driven largely by ferroptosis-induced neuronal death and maladaptive neuroinflammation. Current therapies are limited by poor drug delivery and the narrow scope of single-pathway interventions. Here, we report a biomimetic hybrid nanovesicle (hMLV) engineered to codeliver the ferroptosis inhibitor ferrostatin-1 (Fer-1) and M2 macrophage-derived exosomes, enabling simultaneous suppression of neuronal ferroptosis and reprogramming of the immune microenvironment. The liposomal core encapsulates hydrophobic Fer-1 to enhance solubility and stability, while the exosomal membrane promotes blood-brain barrier penetration, lesion targeting via chemokine receptors, and immune evasion through CD47 expression. Within injured brain tissue, released Fer-1 restores glutathione peroxidase 4 (GPX4) activity, reduces lipid peroxidation, and prevents ferroptotic neuronal death. Concurrently, exosomal cytokines such as interleukin-10 and transforming growth factor-β drive macrophage polarization toward a reparative M2 phenotype, mitigating neuroinflammation. This dual mechanism establishes a positive therapeutic cycle: ferroptosis inhibition dampens inflammatory triggers, while M2 polarization reduces oxidative stress. In a murine TBI model, hMLV treatment conferred superior neuroprotection and functional recovery compared with monotherapies. These findings highlight hMLV as a clinically translatable nanoplatform for synergistic, mechanism-guided intervention in secondary brain injury.

Keywords:  biomimetic nanovesicle; ferroptosis inhibition; immune reprogramming; neuroinflammation modulation; traumatic brain injury (TBI)

DOI:  https://doi.org/10.1021/acsami.6c01290
Tissue Eng Regen Med. 2026 Apr 05.

Regenerative effects of myogenic gene transfected MSC derived exosomes on radiation esophagitis.

Min-Kyung Kim, In Gul Kim, So Young Eom, Yewon Kim, Jin-A Kim, Jungirl Seok, Seok Chung, Hye-Joung Kim, Eun-Jae Chung.

   BACKGROUND: Radiation esophagitis is a common adverse effect of radiotherapy for head and neck cancers, and is marked by irreversible damage and fibrosis of esophageal muscle tissue. Although mesenchymal stem cell (MSC) therapy is emerging as a promising approach for tissue regeneration, clinical translation remains challenging due to issues with cell viability and differentiation in vivo. This study evaluates the regenerative efficacy of exosomes derived from MSCs transfected with myogenic genes (MyoD, Myogenin, Myf6, referred to as Myo-MIX) using a murine model of radiation-induced esophageal fibrosis.
METHODS: Human adipose-derived MSCs were transfected with Myo-MIX plasmids by electroporation, and exosomes were collected from conditioned media using ExoQuick. Nanoparticle tracking analysis and transmission electron microscopy were employed to characterize exosomal size and morphology. A mouse model of localized radiation-induced esophageal injury (10 Gy × 2 fractions) was generated and followed by intramuscular administration of Myo-MIX exosomes. Regenerative and anti-fibrotic outcomes were examined through Masson's trichrome staining, immunohistochemistry (α-SMA, Calponin, CD68), and quantitative RT-PCR.
RESULTS: Treatment with Myo-MIX exosomes resulted in a pronounced decrease in fibrosis and inflammatory response compared to PBS-treated controls and naïve MSC-exosome groups. Enhanced restoration of muscular architecture was observed, accompanied by elevated expression of Calponin and α-SMA, and a reduction in CD68 + macrophage infiltration. Gene expression profiling indicated increased levels of myogenic and anti-fibrotic markers in the Myo-MIX exosome-treated group.
CONCLUSION: Exosomes from myogenic gene-transfected MSCs significantly enhance esophageal muscle regeneration and attenuate fibrosis after radiation-induced damage. This cell-free therapeutic approach holds potential as a novel and practical strategy for addressing radiation esophagitis in patients receiving radiotherapy for head and neck malignancies.

Keywords:  Exosome; Fibrosis; Gene therapy; Head and neck caccer; Radiation therapy

DOI:  https://doi.org/10.1007/s13770-026-00795-4
Adv Healthc Mater. 2026 Apr 09. e05504

Delivery of Engineered BMP2 circRNA via Biomimetic Nanovesicles Enhances Titanium Implant Osseointegration Through Translation-Controlled Osteogenesis.

Yichen Li, Ziyan Guo, Pengyu Zhao, Yan Dong, Mei Yong, Qi Li, Liang Kong, Zhongshan Wang.

  Although mRNA therapy has achieved favorable outcomes, it still faces limitations such as poor stability and short duration of protein expression. In this study, we utilized a covalently closed circular RNA encoding bone morphogenetic protein-2 (BMP2 circRNA), which exhibits exceptional nuclease resistance and an extended half-life, thereby enabling sustained and efficient BMP2 protein expression. The BMP2 circRNA was encapsulated into biomimetic nanovesicles (BNVs) derived from bone marrow mesenchymal stem cells (BMSCs) using co-extrusion technology. These BNVs were then anchored onto the surface of micro-arc oxidized titanium (Ti-MAO) implants via polydopamine (PDA) adhesion, constructing a novel local gene delivery system. In vitro experiments confirmed that this system is not only efficiently internalized by cells but also evades lysosomal degradation, facilitating the sustained release of BMP2 protein. This, in turn, significantly promoted osteogenic gene expression and accelerated mineral deposition. Furthermore, in vivo animal studies demonstrated that the functionalized implant markedly enhanced bone regeneration, increasing both bone volume fraction and bone-to-implant contact. This study successfully integrated the inherent stability of circRNA with a biomimetic delivery strategy, offering an effective approach for improving implant osseointegration.

Keywords:  biomimetic nanovesicles; bone morphogenetic protein‐2; circular RNA; micro‐arc oxidized titanium; osseointegration

DOI:  https://doi.org/10.1002/adhm.202505504
Bioact Mater. 2026 May;59 96-134

Engineered small extracellular vesicles as bioactive materials: Integrating engineering strategies for cargo loading and targeted delivery systems.

Hongtao Xu, Rui Liu, Hao Zhou, Bin Kong, Kai Shen, Tao Zhao, Xiaofeng Du, Hao Zhang, Huanghe Song, Dunming Guo, Xiaoyuan Gu, Qing Wang, Chien-Wei Lee, Guoyong Yin, Yingze Zhang, Wei Chen.

  Small extracellular vesicles (sEVs) are increasingly regarded as a unique class of bioactive materials whose intrinsic membrane composition and nanoscale architecture provide a versatile platform for therapeutic engineering. Rather than passive carriers, sEVs can be actively programmed through diverse strategies to achieve efficient loading, precise targeting, and functional integration with synthetic systems. Endogenous modulation of donor cells-via genetic editing, priming with bioactive glass, cytokine stimulation, or hypoxic cues-enables selective packaging of nucleic acids, proteins, and metabolites into secreted vesicles. Exogenous techniques, including electroporation, sonication, and extrusion, allow controlled incorporation of therapeutic drugs or genome-editing complexes such as CRISPR/Cas. In parallel, surface modifications based on Lamp2b-fusion scaffolds, aptamers, antibodies, and click chemistry confer tissue tropism and extend circulation time. Integration with nanomaterials, scaffolds, and microfluidic platforms further enhances stability, scalability, and reproducibility, positioning sEVs at the intersection of biology and materials science. This review highlights recent advances in engineering sEVs as programmable bioactive materials and discusses their potential to transform regenerative medicine, oncology, and precision therapeutics.

Keywords:  Cargo loading; Extracellular vesicles; Targeted delivery; Therapeutic application

DOI:  https://doi.org/10.1016/j.bioactmat.2025.12.029
Int J Pharm X. 2026 Jun;11 100520

Oral milk-derived exosomes loaded with tafatinib for anti-inflammatory therapy.

Qiao Qiao, Caoganhong Wang, Zhen Mao, Weijun Chen, Weibo Kong, Lipeng Qiu, Huiming Tu.

  Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease primarily affecting the colon and rectum, characterized by complex pathogenesis and clinical challenges, such as disease recurrence and potential malignant transformation. The pan-JAK inhibitor tofacitinib (TOF) has emerged as an effective therapeutic option for inducing and maintaining clinical remission in moderate-to-severe UC. Recent advances in nanomedicine have identified milk-derived exosomes (mEXOs) as promising natural drug delivery vehicles due to their favorable physicochemical properties and biocompatibility. Therefore, an oral TOF-loaded mEXOs system (mEXOs@TOF) was successfully developed, which exhibited favorable pharmaceutical characteristics, including stability, uniform size distribution, high drug-loading capacity, and efficient macrophage uptake. The therapeutic efficacy of mEXOs@TOF was mediated through multifaceted mechanisms including suppression of pro-inflammatory cytokines (IL-6, IFN-γ, NO), elevation of anti-inflammatory IL-10 levels, reduction of reactive oxygen species production, and inhibition of JAK-STAT3 signaling pathway activation. Comprehensive in vitro and in vivo assessments of mEXOs@TOF confirmed the enhanced anti-inflammatory treatment on UC, with no detectable adverse effects. Collectively, the mEXOs@TOF nanodelivery system represents a targeted therapeutic strategy for improving UC treatment.

Keywords:  Milk exosomes; Oral drug delivery; Tofacitinib; Ulcerative colitis

DOI:  https://doi.org/10.1016/j.ijpx.2026.100520
Apoptosis. 2026 Apr 06. pii: 120. [Epub ahead of print]31(4):

NUFIP1-engineered exosomes modulate propofol-induced neurotoxicity in neonatal rats via the ERS apoptotic pathway.

Pengyue Zhao, Yang Yan, Bin Lan, Xingpeng Yang, Yizhao Ma, Yichen Bao, Lin Qi, Xiaohui Du, Songyan Li, Wen Sun.

  Early-life exposure to general anesthetics, particularly propofol, elevates the risk of neurodevelopmental impairment and cognitive sequelae in pediatric populations, representing a pivotal concern in translational neuroanesthesiology. Although preclinical studies have linked propofol to increased developmental neurotoxicity, the underlying molecular mechanisms remain elusive. Our previous work established that nuclear fragile X mental retardation-interacting protein 1 (NUFIP1)-engineered exosomes from human umbilical cord mesenchymal stem cells could mitigate propofol-induced neurotoxicity and neuronal apoptosis in neonatal rats during a critical postnatal window of synaptogenesis (postnatal days 7-14). The present study provides the first mechanistic insights by performing transcriptomic profiling to link this neuroprotection to the endoplasmic reticulum stress (ERS) apoptotic pathway. Importantly, we directly validated key ERS/apoptosis markers and functionally confirmed the pathway's role through pharmacological rescue experiments with Salubrinal. In conclusion, NUFIP1-engineered exosomes regulate propofol-induced nerve injury through the ERS apoptotic pathway, offering novel mechanistic insights with potential implications for addressing pediatric neurodevelopmental impairments.

Keywords:  Apoptosis; Exosomes; NUFIP1; Neurotoxicity; Propofol; Ribophagy

DOI:  https://doi.org/10.1007/s10495-026-02326-x
ACS Nano. 2026 Apr 07.

Exosome-Mitochondrial Hybrid Membrane with Targeted Delivery of CO Prevents Mitochondrial Dysfunction and Pyroptosis against Myocardial Ischemia-Reperfusion Injury.

Lintao Wang, Qianzhi Shi, Chenxiao Jiang, Mengyao Xu, Xinyu Wang, Hao Ren, Xudong Wang, Qijun Fang, Jing Sun, Lina Kang, Xin Chen, Dujuan Sha, Jie Ni.

  Myocardial ischemia-reperfusion (I/R) injury exacerbates cardiac dysfunction and heart failure following clinical revascularization. The main mechanisms involve aberrant accumulation of reactive oxygen species (ROS) that induce mitochondrial dysfunction, trigger pyroptosis, and amplify immune-inflammatory responses. Herein, we developed exosome-mitochondrial hybrid membrane vessels to encapsulate carbon monoxide (EM@CO) for targeted delivery of CO to attenuate myocardial I/R injury. Due to the adhesive properties of exosomes and the homologous mitochondrial targeting capacity of the mitochondrial membrane (MM), EM@CO exhibits sequential targeting from infarcted myocardium to myocardial cell mitochondria. The released CO in mitochondria reduces abnormal mitochondrial ROS generation to maintain mitochondrial function, thereby decreasing mtDNA release and inhibiting pyroptosis in vitro and in vivo. Moreover, a single intravenous injection of EM@CO attenuates inflammatory amplification in cardiac tissue by promoting M1 to M2 macrophage polarization. It can effectively decrease the pro-inflammatory cytokine release and inhibit inflammation, thereby attenuating myocardial infarction and improving cardiac function. In summary, the findings of this study reveal the potential for restoring mitochondrial function through targeted gas therapy to eliminate reactive oxygen species (ROS) and inhibit cellular pyroptosis, which holds promise for ameliorating myocardial ischemia-reperfusion injury.

Keywords:  exosome-mitochondrial hybrid membrane; mitochondrion function; myocardial ischemia-reperfusion injury; pyroptosis; sequential targeted CO gas therapy

DOI:  https://doi.org/10.1021/acsnano.5c21479
Int J Nanomedicine. 2026 ;21 583242

Engineering the Future: Strategic Advances in Extracellular Vesicle-Mediated Drug Delivery Systems.

Xiran Zhang, Xiaomin Zhang.

  Extracellular vesicles (EVs) are lipid bilayer-enclosed nanoparticles naturally secreted by cells that inherently lack replicative capacity and function as endogenous carriers of biological cargo including proteins, nucleic acids, and metabolites for intercellular communication. Leveraging their intrinsic biocompatibility and biomimetic transport properties, EVs have emerged as versatile drug delivery platforms with distinct therapeutic advantages. Recent advancements have developed two precision-engineered derivatives: structurally and cargo-modified engineered EVs, and EV mimetics integrating synthetic nanomaterials. Both types are designed to enhance targeting specificity and therapeutic efficacy, yet their strong intercorrelations frequently cause confusion. This review systematically examines the evolving landscape of EV-based delivery systems by establishing conceptual distinctions between native EVs, engineered EVs, and EV mimetics, while comparatively analyzing their preparation methodologies, clinical translation progress, and performance characteristics as drug carriers. Through systematic discussion of clinical challenges, including safety, clinical feasibility, and cross-laboratory reproducibility, we propose optimization directions integrating artificial intelligence with drug delivery systems, thereby providing insights and methodologies for next-generation EV-inspired therapeutic delivery platforms.

Keywords:  drug delivery system; engineered extracellular vesicles; extracellular vesicle mimetics; extracellular vesicles; synthetic nanoparticles

DOI:  https://doi.org/10.2147/IJN.S583242
Food Res Int. 2026 Jun 01. pii: S0963-9969(26)00699-X. [Epub ahead of print]233(Pt 2): 119022

Orally engineered liver-targeted garlic exosome-like nanovesicles for astaxanthin precise delivery against alcoholic liver disease in mice.

Qinglin Qu, Fan Liu, Huajing Gao, Xiangrui Kong, Xue Gao, Yukun Song, Mingqian Tan, Yannan Chen, Dapeng Li, Xintong Tan.

  Orally targeted strategy of nutrients has attracted obvious attention for reducing side effects and enhancing the intervention efficiency of alcoholic liver disease (ALD). Herein, novel lactobionic acid-modified garlic exosome-like nanovesicles (LA-GELN) were designed to precise delivery astaxanthin (AXT) against alcohol-induced lipid metabolism disorders. The targeted modification of nanovesicles enhanced the encapsulation efficiency of AXT (80.03%). Meanwhile, the encapsulation strategy also improved the solubility and gastrointestinal stability of AXT. In the HepG2 cell model, LA-GELN-AXT demonstrated excellent cellular uptake capacity (Pearson correlation coefficient of 0.87) and effectively alleviated oxidative stress and lipid droplet formation. In vivo studies also demonstrated that 8 h after oral administration, the hepatic fluorescence intensity in the LA-GELN and GELN groups was 1.98-fold and 1.26-fold that of the Nile red group, respectively. In the ALD mouse model, LA-GELN-AXT effectively mitigated oxidative damage, reduced inflammatory cytokine levels, restored mitochondrial function, and further alleviated lipid accumulation. Its mechanism of action was associated with the modulation of the TLR4/MyD88/NF-κB inflammatory signaling pathway and the subsequent alleviation of ALD-induced hepatic metabolic disorders.

Keywords:  Alcoholic liver disease; Astaxanthin; Garlic exosome-like nanovesicles; Liver targeting; Metabolic disorder

DOI:  https://doi.org/10.1016/j.foodres.2026.119022