bims-engexo 2026-09-06 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–09–06
twelve papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Targeted delivery of peptidoglycan hydrolases (PGH) via engineered extracellular vesicles (EVs) to clear intracellular bacterial infections.
Engineered MSC-exosomes as CRISPR-Cas9 delivery vectors for precision immunotherapy.
PEBP1 Regulates Ferroptosis in Acute Glaucoma: Targeted Therapy Using Engineered Exosomes.
Therapeutic Potential of Gene Modified MSC-Exos in Insulin Resistance: Mitochondrial Crosstalk and miRNA Regulation.
Enhanced odontoblast regeneration and anti-inflammatory effects of nanocurcumin-loaded BM-MSC-derived exosomes in an LPS-induced periodontitis rat model.
Synergistic Wound Healing Enhancement by Extracellular Vesicles From Engineered Macrophages and Fibroblasts.
Intranasal L-DOPA/TPP-engineered extracellular vesicles deliver icariin to ameliorate mitochondrial dysfunction with associated sphingolipid remodeling in Alzheimer's disease models.
Extracellular Vesicle Therapies for Diabetic Skin Lesions: Mechanisms, Engineering, and Clinical Translation.
Extracellular vesicles in pharmacology: Innovations in drug delivery and therapeutic applications in cancer.
Engineering Piezo1-Mediated Calcium Signalling for Enhanced Extracellular Vesicle Biogenesis and Cargo Loading.
A novel phage display-identified nucleus pulposus-targeting peptide enhances exosome therapy for intervertebral disc degeneration.
Inhalable biomimetic apoptotic bodies enable targeted LXRα agonist delivery to lung macrophages for acute lung injury therapy.

Mater Today Bio. 2026 Oct;40 103567

Targeted delivery of peptidoglycan hydrolases (PGH) via engineered extracellular vesicles (EVs) to clear intracellular bacterial infections.

Besmira Sabani, Martina Leone, Lynn Gasser, Eric Sumrall, Susanne Meile, Joelle Inderbitzin, Daniel Razansky, Mathias Schmelcher, Martin J Loessner, Rainer Riedl, Steffi Lehmann.

  Bacterial infectious diseases remain a major global health threat due to increasing antibiotic resistance. Further complicating effective treatment, some pathogens such as Staphylococcus aureus persist within host cells. Peptidoglycan hydrolases (PGHs), including bacteriophage-derived endolysins, represent a promising class of novel antimicrobials due to their rapid bacteriolytic activity and low risk of resistance emergence. However, their clinical application is limited by an unfavourable PK profile and inefficient delivery into infected host cells. Here, we engineered extracellular vesicles (EVs) for the targeted, intracellular delivery of GH15, a novel endolysin against S. aureus. GH15-loaded EVs, functionalized with antibodies targeting αvβ3 integrin on bacterially infected cells, efficiently delivered GH15 into S. aureus-positive endothelial cells and macrophages in vitro and eliminated intracellular bacteria. In addition, GH15-loaded EVs promoted the clearance of intracellular bacteria in macrophages of infected zebrafish larvae in vivo. Our findings establish EVs as effective vehicles for intracellular delivery of antimicrobial enzymes and highlight their potential for the treatment of intracellular bacterial infections.

Keywords:  Antibiotic resistance; Drug delivery; Endolysins; Extracellular vesicles; Intracellular bacterial infection; Peptidoglycan hydrolases; Staphylococcus aureus

DOI:  https://doi.org/10.1016/j.mtbio.2026.103567
Front Bioeng Biotechnol. 2026 ;14 1823483

Engineered MSC-exosomes as CRISPR-Cas9 delivery vectors for precision immunotherapy.

Dandan Guo, Wei Zhang, Wenbo Dou, Yitong Yang, Binbin Sun, Mengyu Qiu, Kai Wang, Jianjun Zhai, Shuying Feng.

  Mesenchymal stem cell-derived exosomes (MSC-Exos) combined with CRISPR-Cas9 hold substantial therapeutic potential for immune-mediated diseases, although significant technical obstacles remain. This review presents a comprehensive analysis of strategies for engineering MSC-Exos as delivery vehicles for CRISPR-Cas9, with emphasis on cargo-loading methodologies and surface modifications that enable targeting specific immune cell populations. We examine the mechanistic basis for the therapeutic effects of these engineered platforms and critically assess the challenges impeding clinical translation, including manufacturing scalability, safety concerns, and regulatory considerations. Key areas of focus for this Research Topic-vehicle engineering, cargo packaging efficiency, biological barriers, and in vivo safety-are systematically addressed. Finally, we discuss emerging directions, including next-generation gene editors and stimulus-responsive biomaterials. This review provides a balanced framework for advancing MSC-Exos-based nanoplatforms toward precision gene therapies for immune disorders.

Keywords:  CRISPR-Cas9; autoimmune diseases; clinical translation; gene editing; immunotherapy; mesenchymal stem cell-derived exosomes; targeted delivery; vehicle engineering

DOI:  https://doi.org/10.3389/fbioe.2026.1823483
FASEB J. 2026 Sep 15. 40(17): e72269

PEBP1 Regulates Ferroptosis in Acute Glaucoma: Targeted Therapy Using Engineered Exosomes.

Yijia Huang, Di Gong, Junhong Guo, Wei Huang, Tingyu Hu, Shengbin Tang, Li Li, Bingkai Feng, Kuanrong Dang, Simin Deng, Yong Liu, Chunyan Tan, Fei Yao, Jiantao Wang.

  Glaucoma is the leading cause of irreversible blindness worldwide, primarily driven by the progressive loss of retinal ganglion cells (RGCs) under pathological high intraocular pressure (ph-IOP). Despite the established role of ferroptosis in RGC degeneration, specific molecular targets that can be used for clinical intervention still need to be optimized, and the slow onset of conventional gene therapy vectors is incompatible with the acute clinical course of glaucoma. Here, we integrate single-cell RNA sequencing and spatial transcriptomics to profile the dynamic transcriptomic landscape of the rat retina across acute, subacute, and chronic stages of ph-IOP injury. Through ferroptosis-focused screening of an early-activated RGC gene cluster, we identify the lipid metabolism regulator phosphatidylethanolamine-binding protein 1 (PEBP1) as a candidate mediator of RGC ferroptosis. We demonstrate that Pebp1 is specifically upregulated in injured RGCs with a trajectory mirroring ferroptosis pathway activation, and that AAV-mediated Pebp1 knockdown suppresses ferroptosis through the GPX4/ACSL4 signaling axis, thereby preserving RGC survival, retinal structure, and visual function. To overcome the critical time-window bottleneck-the several weeks delay required for AAV-mediated silencing versus the rapid, irreversible RGC loss in acute glaucoma-we engineer Exosomes-siPebp1, a mesenchymal stem cell-derived exosome system loaded with siPebp1, which enables immediate single-dose intervention post-injury. This system exhibits efficient RGC uptake, prolonged intraocular retention, and robust target gene silencing, and, in a head-to-head comparison, significantly outperforms unloaded exosomes, liposomal formulations, and AAV vectors in RGC protection, without detectable acute systemic or local toxicity. Collectively, this study implicates Pebp1 in ph-IOP-associated RGC ferroptosis and supports exosome-mediated siRNA delivery as a rapid, cell-free intervention strategy for acute glaucomatous injury.

Keywords:  ferroptosis; glaucoma; neuroprotection; phosphatidylethanolamine‐binding protein 1; siRNA delivery; single‐cell and spatial transcriptomics; stem cell‐derived exosomes

DOI:  https://doi.org/10.1096/fj.202602807R
J Cell Mol Med. 2026 Sep;30(17): e71342

Therapeutic Potential of Gene Modified MSC-Exos in Insulin Resistance: Mitochondrial Crosstalk and miRNA Regulation.

Qinghua Jia, Bing Li, Yuan Xing, Yuanyuan Zhang, Baodong Gao, Xiangying Li, Xiaoqin Ha.

  Insulin resistance (IR) is the key driver of type 2 diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and cardiometabolic disorders. Mesenchymal stem cell-derived exosomes (MSC-Exos) as a potent cell-free alternative can deliver miRNAs, proteins, and mitochondrial regulators to reactivate the IRS1/PI3K/Akt/GLUT4 axis. Beyond restoring insulin signalling, these vesicles can protect β-cells, alleviate endoplasmic reticulum stress, rescue mitochondrial mitophagy and respiration. The genetic engineering strategies including improving the expression of miR-21, miR-3075, or Sirtuin-3, and silencing miR-29b-3p amplify the therapeutic efficacy. However, scalable good manufacturing practice production, long-term safety of modified products, and advanced therapy medicinal product regulation are still needed to overcome. This review will introduce the potential of gene-modified MSC-Exos and miRNAs targeting insulin signalling and mitochondrial rescue, which have shown a shift from symptomatic relief to precision disease-modifying therapy for IR.

Keywords:  gene modification; insulin resistance; mesenchymal stem cells; microRNA; mitochondrion; precision medicine; type 2 diabetes mellitus; exosomes

DOI:  https://doi.org/10.1111/jcmm.71342
BMC Oral Health. 2026 Sep 03. pii: 1669. [Epub ahead of print]26(1):

Enhanced odontoblast regeneration and anti-inflammatory effects of nanocurcumin-loaded BM-MSC-derived exosomes in an LPS-induced periodontitis rat model.

Nehad M Abd-Elmonsif, Ahmed Morsy, Mona El Deeb.

   BACKGROUND: Periodontitis is commonly known as a chronic inflammatory disease which adversely affects pulpal and periodontal tissues, including odontoblasts. Bone marrow mesenchymal stem cell-derived exosomes (BM-MSC-Exo) and nanocurcumin (NCUR) possess anti-inflammatory and regenerative properties; however, their combined effects on odontoblasts remain insufficiently explored. The research target was to assess the histological, histochemical, and anti-inflammatory effects of BM-MSC-Exo and NCUR-loaded BM-MSC-Exo on odontoblasts of LPS-induced periodontitis in rats.
METHODS: Twenty-eight male albino rats were assigned at random into four groups (n = 7 each): control, periodontitis, periodontitis treated with BM-MSC-Exo, and periodontitis treated with NCUR-loaded BM-MSC-Exo. Periodontitis was induced via intra-periodontal LPS injections. Histological evaluation was performed using hematoxylin and eosin staining, and collagen synthesis was analyzed using Masson's trichrome stain. Morphometric analysis of newly formed collagen and enzyme-linked immunosorbent assay (ELISA) of interleukin-10 (IL-10) levels were conducted.
RESULTS: Untreated periodontitis caused marked odontoblastic degeneration, reduced predentin thickness, and decreased collagen formation. Treatment with BM-MSC-Exo significantly improved odontoblastic architecture, enhanced collagen deposition, and increased IL-10 expression. NCUR-loaded BM-MSC-Exo demonstrated superior regenerative and anti-inflammatory effects, characterized by improved odontoblastic organization, increasing the area of newly formed collagen, and significantly elevated IL-10 levels compared with all other groups (p < 0.001).
CONCLUSIONS: BM-MSC-Exo exerts regenerative effects on odontoblasts in periodontitis, which are further enhanced by NCUR loading. NCUR-loaded BM-MSC-Exo declares an encouraging cell-free medicinal strategy for regeneration of periodontal and pulpal tissues.

Keywords:  Interleukin-10; Mesenchymal stem cell exosomes; Nanocurcumin; Odontoblasts; Periodontitis; Regenerative dentistry

DOI:  https://doi.org/10.1186/s12903-026-09697-2
J Biomed Mater Res A. 2026 Sep;114(9): e70126

Synergistic Wound Healing Enhancement by Extracellular Vesicles From Engineered Macrophages and Fibroblasts.

Ping Liang, Jialin Ye, Kaiyang Lin, Qinghua Luo, Haisu Zheng, Yuyao Hu, MingLang Zou, Yanting Huang, Sifang Wu, Qi Sun, Yansong Guo, Zuquan Weng.

  Severe wound healing impairment risks persistent tissue damage and even necrosis. Cell-free exosome therapy demonstrates significant potential in wound healing due to its high efficacy and micro-volume characteristics. However, its clinical-scale translation faces challenges including low yield, limited sources, functional monotony, and low bioavailability. We developed a lentiviral co-engineering strategy introducing exosome secretion-related genes into macrophage and fibroblast cell lines, achieving stable, high-yield (twofold increase) exosome production. Co-engineered extracellular vesicles (EVs) demonstrated enhanced cellular uptake and synergistically upregulated pro-angiogenic (HIF-1α, VEGF-A) and anti-inflammatory (IL-4, IL-10) factors. In a cell model and murine full-thickness wound model, the combination of EVs from both sources potently accelerated healing, promoting re-epithelialization and collagen deposition while orchestrating an anti-inflammatory response via TNF-α/IL-1β downregulation and IL-10 upregulation. In summary, co-cultured EVs not only exhibit high yield and purity but also demonstrate potent pro-angiogenic, anti-inflammatory, and antioxidant effects, effectively promoting wound healing, epithelial tissue regeneration, and collagen deposition. This study proposes an innovative and highly efficient method for synergistically regulating the production of EVs from cellular systems, providing promising research resources for their application in wound healing and medical esthetics. It also offers crucial insights for investigating the underlying mechanisms.

Keywords:  extracellular vesicles; fibroblast; lentiviral transfection; macrophage; wound healing

DOI:  https://doi.org/10.1002/jbm.a.70126
Mater Today Bio. 2026 Oct;40 103563

Intranasal L-DOPA/TPP-engineered extracellular vesicles deliver icariin to ameliorate mitochondrial dysfunction with associated sphingolipid remodeling in Alzheimer's disease models.

Beibei Wu, Junyong Wu, Lemei Zhu, An Li, Yangbo Fu, Zuchao Lei, Dahua Wu, Weijun Peng, Le Xie.

  Alzheimer's disease (AD) is associated with mitochondrial dysfunction, oxidative stress, and disrupted lipid homeostasis, but the therapeutic translation of mitochondrial-protective agents remains limited by inefficient brain delivery, insufficient neuronal selectivity, and poor subcellular precision. Here, we developed an intranasal extracellular vesicle formulation (L-DOPA/TPP-EV-ICA) by loading icariin (ICA) into mesenchymal stem cell-derived extracellular vesicles and post-inserting DSPE-PEG-Levodopa and TPP-PEG-PE to enhance nasal environment, neuronal association, and mitochondria-associated intracellular enrichment. The engineered vesicles retained EV-like morphology, showed measurable ICA encapsulation, and maintained colloidal stability under the tested storage and simulated nasal conditions. In a human nasal epithelial Transwell model, L-DOPA/TPP-EV-ICA showed greater neuronal uptake than unmodified EVs without detectable disruption of epithelial barrier integrity and exhibited preferential colocalization with mitochondria-associated structures after cellular internalization. In Aβ-injured neuronal cells, L-DOPA/TPP-EV-ICA treatment reduced mitochondrial oxidative stress and mPTP opening, improved membrane potential, and enhanced ATP production and redox-related parameters. Following intranasal administration, the engineered formulation generated stronger and more persistent brain-associated fluorescence and showed preferential association with NeuN-positive cells. In APP/PS1 mice, treatment improved cognitive performance, and attenuated histopathological and mitochondrial abnormalities. Integrated proteomic, metabolomic analyses, and protein-level analyses further identified treatment-associated alterations in sphingolipid-related pathways. These findings support L-DOPA/TPP-EV-ICA as a promising preclinical intranasal EV platform for improving mitochondrial function and modulating sphingolipid-associated alterations in AD-related models.

Keywords:  Alzheimer's disease; Extracellular vesicles; Icariin; Intranasal delivery; Mitochondria-associated localization; Sphingolipid metabolism

DOI:  https://doi.org/10.1016/j.mtbio.2026.103563
Int J Nanomedicine. 2026 ;21 626719

Extracellular Vesicle Therapies for Diabetic Skin Lesions: Mechanisms, Engineering, and Clinical Translation.

Tietao Di, Hexiang Wu, Po Yang, Yao Pan, Yimei Zhang, Yongxiang Zhang.

  Diabetic foot ulcers and other chronic diabetic skin lesions persist because vascular insufficiency, neuropathy, infection, oxidative stress, dysregulated inflammation, and impaired stromal and epithelial repair act concurrently. Extracellular vesicles (EVs), including exosome-enriched preparations, can deliver proteins, lipids, and regulatory RNAs to multiple wound-resident cell types and therefore offer a cell-free strategy for this multifactorial pathology. This review examines recent evidence for EV-based therapy across inflammatory resolution, angiogenesis, fibroblast and keratinocyte recovery, extracellular matrix remodeling, redox and mitochondrial homeostasis, and protection from ferroptosis and neutrophil extracellular trap-associated injury. It also evaluates source selection, cargo and surface engineering, and local delivery systems such as hydrogels, dressings, and microneedles. Preclinical studies consistently report improved wound closure and tissue repair, whereas human evidence remains limited to early clinical and biomarker studies. Translation is constrained by product heterogeneity, donor and culture effects, isolation-dependent composition, inconsistent dose metrics, uncertain potency assays, storage and scale-up requirements, and incomplete regulatory alignment. Progress will require phenotype-matched products, MISEV-aligned characterization, GMP-compatible manufacturing, mechanism-linked release assays, and trials that test EVs as adjuncts to high-quality standard care using durable closure and recurrence as clinically meaningful outcomes.

Keywords:  diabetic foot ulcer; diabetic wound; exosomes; extracellular vesicles; hydrogel; nanomedicine

DOI:  https://doi.org/10.2147/IJN.S626719
Br J Pharmacol. 2026 Sep 02.

Extracellular vesicles in pharmacology: Innovations in drug delivery and therapeutic applications in cancer.

Evangelia Pantazaka, Georgios Sivvas, Evangelia Papadimitriou, Constantinos M Mikelis.

  Extracellular vesicles (EVs) are a diverse population of membrane nanoparticles secreted by nearly all cell types, playing a key role in intercellular communication by transferring bioactive macromolecular cargo. In cancer, EVs shape both the local tumour microenvironment and distant premetastatic niches. They are essential regulators of tumour initiation, progression, immune modulation, angiogenesis and metastatic dissemination. Due to their abundance in biofluids, EVs have attracted attention as diagnostic and prognostic biomarkers for early detection and assessment of therapeutic response. Additionally, EVs represent a promising therapeutic platform for delivering chemotherapeutic agents, nucleic acids and gene-editing tools, with enhanced specificity and reduced systemic toxicity. This review summarises current therapeutic applications of EVs across breast, lung, colorectal, prostate and pancreatic cancers and glioblastoma. Key findings are presented for each formulation, with emphasis on the EV physicochemical properties and engineered modifications, their cargo and mechanisms underlying their biological effects. Although the clinical translation of EV-based advances remains limited and challenging, this review highlights significant preclinical findings and examples of clinical trials where EVs have been used as therapeutic agents.

Keywords:  drug delivery system; drug resistance; extracellular vesicles; therapeutic application; types of cancer

DOI:  https://doi.org/10.1111/bph.70616
J Extracell Biol. 2026 Sep;5(9): e70182

Engineering Piezo1-Mediated Calcium Signalling for Enhanced Extracellular Vesicle Biogenesis and Cargo Loading.

Najla A Saleh, Rozita Shafiq, Amanda P Cicerone, Sadhana Kilangodi, Hayden Hartwig, George I Mias, Guangqing Lu, Jun R Huh, Weiping Li, Cheri X Deng, Masamitsu Kanada.

  Cell-derived extracellular vesicles (EVs) are promising nanocarriers for therapeutic delivery platforms owing to their biocompatibility and capacity to protect and efficiently transport bioactive molecules. However, EV-based therapeutics remain constrained by inefficient cargo loading and low production yields, which limit scalable biomanufacturing. To overcome these limitations, we exploited the use of the mechanosensitive ion channel Piezo1 as a robust regulator of EV biogenesis using HEK293FT cells co-transfected with Piezo1 and the bioluminescent EV reporter PalmReNL. Activation of Piezo1 with Yoda1 (30 µM) increased PalmReNL-EV release by 3-fold, while GsMTx4 inhibited EV release by 80.7%. This effect was unaffected by removal of extracellular Ca2+ but was suppressed by intracellular Ca2+ chelation with BAPTA-AM, indicating a reliance on intracellular Ca2+ mobilisation. Small EVs (sEVs) from Piezo1-activated cells were purified by anion exchange chromatography and analysed by proteomics, identifying 48 proteins exclusively in Piezo1-induced sEVs preparations among 148 total detected, including cytoskeletal and stress-related factors, while preserving enrichment of extracellular matrix (ECM) structural components prominent in both conditions. Yoda1 treatment increased the release of both large EVs (lEVs) and sEVs, with a particularly pronounced increase in sEV production. As a proof of concept for therapeutic cargo delivery, Yoda1 stimulation increased the incorporation of exogenously expressed interleukin-10 (IL-10) into sEVs by up to 4-fold, and the bioactivity of sEV-associated IL-10 was validated using IL-10-CyCLoPs reporter cells. However, exposing Piezo1-overexpressing cells to 30 µM Yoda1 markedly delayed cell adhesion and spreading, indicating that excessive Piezo1 activation may constrain sustained production of therapeutic sEVs. Collectively, these results identify mechanotransduction as a key regulator of sEV biogenesis and underscore the need for precise temporal control, potentially achievable through ultrasound-based modulation, for the rational engineering of next-generation sEV therapeutics.

Keywords:  Piezo1; Yoda1; bioluminescence; calcium signalling; extracellular vesicle; proteomics

DOI:  https://doi.org/10.1002/jex2.70182
Colloids Surf B Biointerfaces. 2026 Aug 24. pii: S0927-7765(26)00668-5. [Epub ahead of print]269 116080

A novel phage display-identified nucleus pulposus-targeting peptide enhances exosome therapy for intervertebral disc degeneration.

Youyou Shao, Yucheng Xue, Jinhao Zhang, Hua Li, Zilong Li, Peng Lin, Zhiyi Zhou.

  Intervertebral disc degeneration (IVDD) is driven by progressive loss of nucleus pulposus cell (NPC) homeostasis, yet therapeutic delivery to NPCs remains limited by the avascular, dense disc microenvironment and the lack of cell-selective ligands. Here, cell-based phage display identified a novel NPC-affinitive peptide, EYFNSPKYDLYR (NTP), which exhibited preferential affinity for NPCs over annulus fibrosus cells and endplate chondrocytes. NTP was incorporated onto mesenchymal stem cell-derived exosomes (MSC-exo) through DSPE-PEG-mediated post-insertion to generate NTP-modified, NPC-targeted MSC-derived exosomes (NT-EXO). NT-EXO retained typical exosomal characteristics while exhibiting enhanced NPC uptake and improved early intradiscal retention. In TBHP-injured NPCs, NT-EXO restored ACAN and COL II expression and reduced MMP13 expression. Molecular analyses further showed partial restoration of miR-142-3p, miR-199a, and miR-217, accompanied by regulation of their reported downstream molecules and attenuation of endoplasmic reticulum stress- and apoptosis-associated transcriptional responses. In a rat puncture-induced IVDD model, NT-EXO improved MRI degeneration grade, disc architecture, proteoglycan preservation, and matrix-marker expression more effectively than unmodified MSC-exo. These findings establish NTP as a functional NPC-targeting ligand and provide preclinical proof-of-concept that cell-selective surface engineering can improve exosome delivery and therapeutic performance in IVDD.

Keywords:  Exosomes; Intervertebral disc degeneration; Nucleus pulposus targeting; Phage display; Surface Engineering

DOI:  https://doi.org/10.1016/j.colsurfb.2026.116080
Colloids Surf B Biointerfaces. 2026 Aug 26. pii: S0927-7765(26)00703-4. [Epub ahead of print]269 116115

Inhalable biomimetic apoptotic bodies enable targeted LXRα agonist delivery to lung macrophages for acute lung injury therapy.

Yue Li, Xuran Ding, Xiying Jin, Taotao Zou, Zan Yong, Hu Li, Haobo Ge, Yihua Yang, Yabing Hua, Yuan Lu, Ziming Zhao, Yuan He.

  Acute lung injury (ALI) is a common critical illness driven by uncontrolled pulmonary inflammation, with hyperactivated macrophages sustaining pro-inflammatory cytokine release. Activation of liver X receptor α (LXRα) can suppress inflammatory gene expression. However, clinical translation of LXRα agonists such as T0901317 (T09) is limited by off-target effects, particularly hepatotoxicity. Here, we developed a biomimetic controlled-release platform (AB/NPs@T09) using mesenchymal stem cell (MSC)-derived apoptotic bodies (ABs) as natural carriers for T09. The structural properties of ABs facilitated macrophage uptake via the efferocytosis pathway. Inhalation administration of AB/NPs@T09 enabled dual organ-cell targeting, increasing pulmonary drug accumulation while markedly reducing liver distribution. In an ALI mouse model, inhaled AB/NPs@T09 at a low dose (1 mg/kg) achieved anti-inflammatory efficacy comparable to that of high-dose intraperitoneal injection (10 mg/kg), without inducing hepatotoxicity. The biomimetic platform presented here not only offers a new avenue for therapeutic intervention in clinical ALI, but also establishes a generalizable strategy for repurposing potent yet toxic small molecules in inflammatory diseases.

Keywords:  Acute lung injury; Apoptotic body; Inhalation administration; LXRα agonist; Mesenchymal stem cells

DOI:  https://doi.org/10.1016/j.colsurfb.2026.116115