bims-engexo 2026-04-26 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–04–26
fifteen papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Bioengineered anti-EpCAM-guided exosome nanocarriers delivering Foxp3 agonist butyrate achieve tissue-specific immunomodulation in autoimmune Sjögren's syndrome.
Delivery of HSP70 mRNA via exosomes ameliorates sleep deprivation-induced cognitive impairments in mice.
M2 macrophage-derived exosomes deliver NGF-modified mRNA to promote comprehensive corneal repair.
Exosomes as Emerging Nanocarriers for Targeted Cancer Therapy.
A dual-functional engineered exosome-laden hydrogel redirects endogenous neural stem cell fate for spinal cord injury repair.
Cargo-driven extracellular vesicles as pharmaceutical nanocarriers: A pharmaceutics-oriented comparison of animal exosomes and plant-derived exosome-like nanoparticles.
Exosome-facilitated nanoplatform for enhanced antibiotic delivery to eradicate intracellular multidrug-resistant Escherichia coli in neonatal sepsis.
Recent Progress in Exosome-Derived Nanocarriers for Breast Cancer Therapy: Advances, Translational Barriers, and Scale-Up Considerations.
Application of hybrid exosomes-mediated targeted delivery system for sinomenine hydrochloride in rheumatoid arthritis therapy.
Germ cell-directed exosomal delivery enables in vivo genetic modification in birds.
Engineered small extracellular vesicles provide low-dose salidroside delivery to attenuate retinal ganglion cell degeneration.
Turmeric-derived exosome-coated ZIF-8 nanoplatform for targeted delivery of TGF-β1 siRNA in the treatment of liver fibrosis.
Intelligent plant exosomes synergize miRNAs and cisplatin for spatiotemporally precise multimodal treatment for TNBC with high safety.
Microcarriers encapsulating COL1A1 mRNA-loaded nanovesicles for skin photoaging treatment.
TeSe nanoparticle-integrated exosomes for accelerated diabetic Pressure ulcer healing via NIR-II triggered synergy.

J Nanobiotechnology. 2026 Apr 21.

Bioengineered anti-EpCAM-guided exosome nanocarriers delivering Foxp3 agonist butyrate achieve tissue-specific immunomodulation in autoimmune Sjögren's syndrome.

Bailing Tian, Qiyu Li, Bohan Chang, Shan Zhao.

  Primary Sjögren's syndrome (pSS) is characterized by salivary gland-centered immune dysregulation, in which an imbalanced T follicular helper (Tfh)/T follicular regulatory (Tfr) axis drives aberrant follicular responses and glandular dysfunction. In this study, we developed an engineered exosome-based therapeutic platform (Exo@But-αEpCAM) by combining CD4+ T cell-derived exosomes, anti-EpCAM antibody-mediated targeting, and sodium butyrate as a Foxp3 agonist. The engineered exosomes exhibited stable antibody modification and efficient drug loading while preserving vesicle integrity and biosafety. Under inflammation-mimicking conditions relevant to pSS, Exo@But-αEpCAM displayed microenvironment-sensitive drug release. In vitro studies using peripheral blood mononuclear cells (PBMCs) from patients with pSS demonstrated that Exo@But-αEpCAM effectively restored the Tfh/Tfr balance by enhancing Foxp3-associated regulatory pathways and suppressing Tfh-related signaling, leading to reduced B cell activation. In a murine model of pSS, targeted exosome treatment preferentially accumulated in salivary glands, significantly improved salivary secretion, alleviated histopathological inflammation, and re-established local immune homeostasis without inducing systemic toxicity. Mechanistically, transcriptomic and proteomic analyses revealed that Exo@But-αEpCAM attenuated Tfh-driven follicular responses through inhibition of the IL-21R/STAT3 signaling axis. Collectively, this work presents a targeted and immunoregulatory exosome-based strategy that reconstructs immune homeostasis rather than broadly suppressing immunity, providing a promising therapeutic approach for pSS.

Keywords:  Exosome Engineering; Foxp3 Agonist; Primary Sjögren’s Syndrome; T Follicular Helper /T Follicular Regulatory Axis; Tissue-Targeted Delivery

DOI:  https://doi.org/10.1186/s12951-026-04373-7
Transl Psychiatry. 2026 Apr 24.

Delivery of HSP70 mRNA via exosomes ameliorates sleep deprivation-induced cognitive impairments in mice.

Zhenming Kang, Guoshao Zhu, Changsheng Su, Xianmei Zhong, Jianchuan Lin, Yiqin Lin.

Chronic sleep deprivation impairs cognition and triggers neuroinflammation, but effective molecular therapies are lacking. Heat shock protein 70 (HSP70) offers neuroprotection, though its delivery across the blood-brain barrier remains a challenge. This study investigates exosomes as a vehicle to enhance brain delivery of HSP70 for treating chronic sleep deprivation. We engineered HEK293T cells to stably express HSP70 mRNA and the brain-targeting RVG-Lamp2b fusion protein, generating HSP70@ExoRVG exosomes. These were characterized via transmission electron microscopy, nanoparticle tracking analysis, and Western blotting. In vitro uptake and HSP70 expression were assessed in neural progenitor cells (NPCs). In vivo efficacy was evaluated in a sleep-deprived mouse model using behavioral tests and molecular analyses of inflammatory and neurotrophic markers. HSP70@ExoRVG exosomes efficiently delivered HSP70 mRNA to NPCs, increasing intracellular HSP70 protein. In vivo, systemic administration restored memory performance, reduced hippocampal TNF-α, IL-6, and IL-1β levels, and increased IL-10. Treatment also elevated brain-derived neurotrophic factor and phosphorylated CREB, indicating enhanced neurotrophic signaling. These effects surpassed those of non-targeted or empty exosomes. Engineered exosomes enabled effective brain-targeted HSP70 mRNA delivery, reversing cognitive and inflammatory consequences of sleep deprivation. To our knowledge, this is the first demonstration of RVG-modified exosomes successfully delivering mRNA (rather than siRNA or miRNA) for the treatment of sleep deprivation-induced deficits. HSP70@ExoRVG offers a promising, noninvasive therapeutic strategy for sleep-related neurodegenerative conditions and highlights the potential of exosome-based mRNA delivery systems.

DOI: https://doi.org/10.1038/s41398-026-04044-z
J Control Release. 2026 Apr 17. pii: S0168-3659(26)00333-0. [Epub ahead of print] 114930

M2 macrophage-derived exosomes deliver NGF-modified mRNA to promote comprehensive corneal repair.

Danni Gong, Huan Chen, Huijing Wang, Nevin Witman, Yang Lu, Yao Fu, Wei Fu.

The cornea is a unique tissue vital for vision but susceptible to various injuries. Given this complexity, effective regeneration following severe damage requires the coordinated restoration of multiple tissue components, underscoring the need for innovative therapeutic strategies. mRNA technology has emerged as a transformative platform for protein delivery and therapeutic intervention. Chemically modified mRNA (modRNA), with its enhanced stability and reduced immunogenicity, enables transient yet highly efficient protein expression, positioning it as a powerful tool for therapeutic applications. Successful mRNA delivery requires optimized vectors, among which exosomes represent ideal carriers due to their natural anti-inflammatory and reparative properties, high loading capacity, and intrinsic targeting ability. Here, we harnessed M2 macrophage-derived exosomes (M2-Exos) to deliver NGF modRNA (modNGF) for multidimensional corneal repair. This combined delivery system demonstrated robust protein expression, simultaneously promoting tissue regeneration while suppressing inflammation and neovascularization in alkali-burned corneas. Single-cell RNA sequencing further revealed that the system effectively restores injury-induced cellular heterogeneity, promotes epithelial regeneration, reprograms immune cells, and enhances corneal nerve regeneration through neuroglial cell proliferation and modulation. Our findings underscore the synergistic therapeutic effects of M2-Exos and modNGF, establishing this innovative delivery platform as a promising strategy for ocular surface diseases and broader regenerative medicine applications.

DOI: https://doi.org/10.1016/j.jconrel.2026.114930
Int J Nanomedicine. 2026 ;21 585042

Exosomes as Emerging Nanocarriers for Targeted Cancer Therapy.

Yao Du, Di Liu, Jiaxing Liu, Jinling Yu, Zhixiong Hao, Manru Zhang, Jianwen Li, Xueqiang Peng.

  Exosomes are nanoscale lipid bilayer vesicles secreted by eukaryotic cells into biological fluids. As an important subtype of extracellular vesicles, they can mediate intercellular material exchange and signal transmission by carrying bioactive substances such as proteins, nucleic acids, and lipids, and participate in the maintenance of physiological homeostasis and the regulation of pathophysiological processes in the body. These biological characteristics make exosomes less likely to be recognized and cleared by the immune system after entering the human body, nor do they cause obvious immune rejection reactions, laying the foundation for their use as delivery carriers. Through engineering techniques, they can be modified, and nucleic acids, small molecule drugs, and other substances can be precisely encapsulated inside exosomes through artificial intervention, forming "exosome-treatment payload" complexes. These complexes can take advantage of the properties of exosomes to significantly enhance their permeability in human tissues and cells, easily cross biological barriers, and promote the enrichment of treatment payloads in specific sites such as tumor tissues, thereby effectively optimizing treatment outcomes. However, the current application of exosomes is still limited by low separation and purification efficiency, high preparation costs, and easy damage to vesicle structure, and the clinical transformation process needs to be accelerated. This review focuses on the latest progress in the research of exosome-targeted delivery platforms, combines existing exosome drug loading technologies, and analyzes the clinical application potential and core challenges of this delivery system in cancer treatment, aiming to provide research directions for the development and clinical transformation of exosome-mediated anti-tumor targeted therapy strategies.

Keywords:  cancer; cargo loading; drug delivery system; exosome

DOI:  https://doi.org/10.2147/IJN.S585042
Bioact Mater. 2026 Aug;62 899-919

A dual-functional engineered exosome-laden hydrogel redirects endogenous neural stem cell fate for spinal cord injury repair.

Wenxiang Li, Wencan Zhang, Han Zheng, Yang Zhang, Yanbin Feng, Yujia Xie, Xuanrui Liu, Mingshan Liu, Xiaohong Kong, Ning Ran, Shiqing Feng.

  Spinal cord injury (SCI) repair is severely restricted by a hostile post-injury microenvironment that drives endogenous neural stem cells (eNSCs) toward astroglial scar formation rather than neuronal regeneration. Here, we developed a dual-functional "molecule-carrier-scaffold" strategy that combines engineered exosomes with a sustained-release hydrogel to simultaneously remodel the inflammatory niche and redirect eNSCs fate. Human umbilical cord mesenchymal stem cell-derived exosomes were engineered to display a neurotrophic factor cocktail (GDNF/NT3/IGF1; termed EXOGNI) and then incorporated into an injectable, in situ photocrosslinkable hydrogel composed of ionic liquid-modified cellulose nanocrystal-reinforced methacrylated silk fibroin (CNCs/SilMA). The resulting EXOGNI@CNCs/SilMA scaffold exhibited a biomimetic porous architecture, spinal cord-compatible mechanical properties, and sustained local release of exosomes during the acute-subacute repair window. In a mouse complete spinal cord transection model, a single implantation of EXOGNI@CNCs/SilMA attenuated acute neuroinflammation and promoted endogenous repair. Lineage tracing showed that the majority of lesion-region Tuj1+ cells were derived from the traced endogenous lineage, and EXOGNI@CNCs/SilMA significantly reduced astrocytic differentiation while increasing neuronal and oligodendroglial lineage outputs. Mechanistically, EXOGNI acted through a dual route: uptake by macrophages/microglia contributed to inflammatory niche modulation, while direct uptake by eNSCs supported fate instruction. Inhibitor studies further indicated that PI3K-AKT and Wnt/Ca2+-CaMKII signaling functioned as parallel pro-differentiation modules, with reduced sustained β-catenin signaling associated with neuronal lineage commitment. These cellular and molecular changes were accompanied by improved motor/sensory recovery and electrophysiological conduction. Collectively, this engineered exosome-loaded hydrogel provides a combinatorial biomaterial platform that reshapes the inhibitory SCI niche and harnesses endogenous neural stem cell-based repair.

Keywords:  Cell fate redirection; Endogenous neural stem cells; Engineered exosomes; Neural regeneration; Spinal cord injury; Sustained-release hydrogel scaffold

DOI:  https://doi.org/10.1016/j.bioactmat.2026.03.023
Int J Pharm X. 2026 Jun;11 100530

Cargo-driven extracellular vesicles as pharmaceutical nanocarriers: A pharmaceutics-oriented comparison of animal exosomes and plant-derived exosome-like nanoparticles.

Hongfeng Xu, Jin Zhang, Meng Li.

  Exosomes and plant-derived exosome-like nanoparticles (PELNs) are increasingly investigated as biologically derived nanocarriers that can couple cargo protection with biointerface-enabled transport. From a pharmaceutics standpoint, their therapeutic performance is often cargo-governed (e.g., microRNAs and proteins) and is ultimately constrained by delivery determinants such as stability, biodistribution, cellular uptake, and intracellular trafficking. In this review, we compare animal-derived exosomes (ADEs) and PELNs through a formulation-centric lens, emphasizing how source-dependent molecular composition shapes critical delivery behaviors and translational feasibility. We reorganize representative preclinical evidence into pharmaceutics-relevant delivery scenarios-including systemic/vascular targeting, blood-brain barrier transport, oral gastrointestinal delivery, and tumor microenvironment modulation-to connect cargo identity with exposure-site interactions and pharmacodynamic outcomes. We further discuss engineering strategies for improving payload control, targeting precision, and dosing accuracy, including endogenous enrichment, exogenous loading, and surface functionalization, while highlighting scale-up and safety considerations introduced by modification. Finally, we delineate translational priorities required to advance exosome-based products toward clinical development: standardized dose metrics (particle- and cargo-normalized), quantitative PK/biodistribution-PD relationships, potency assays and critical quality attributes (CQAs), manufacturing consistency under GMP, and regulatory-compliant characterization. Collectively, this review reframes ADEs and PELNs as cargo-driven pharmaceutical delivery systems and provides a practical roadmap for translation, with particular attention to the oral and scalable potential of PELNs.

Keywords:  5-Fluorouracil; Cholesterol; Corynoxine-B; Curcumin; Digalactosyldiacylglycerol; Doxorubicin; Drug delivery systems; Exosomes; MicroRNA and protein cargo; Monogalactosyldiacylglycerol; Oral bioavailability; Pharmaceutical translation; Phosphatidylcholine; Phosphatidylserine; Plant-derived exosome-like nanoparticles; Sphingomyelin

DOI:  https://doi.org/10.1016/j.ijpx.2026.100530
Int J Pharm. 2026 Apr 20. pii: S0378-5173(26)00318-2. [Epub ahead of print] 126870

Exosome-facilitated nanoplatform for enhanced antibiotic delivery to eradicate intracellular multidrug-resistant Escherichia coli in neonatal sepsis.

Pallabi Chatterjee, Nimbal Kalita, Mukesh Kumar Gupta, Anamika Singh, Utkarsh Jain.

  Neonatal sepsis is a pathogenic infection with an estimated global fatality rate of 18%, poses a greater threat in preterm infants, where early-onset cases often result from vertical transmission from the maternal genital tract. Conventional high-dose antibiotic therapy may lead to adverse effects and limited therapeutic efficiency due to suboptimal intracellular delivery and interactions with extracellular components before effective cellular uptake. To overcome this limitation, exosome-based nanocarriers deliver antibiotics directly into cells, preventing systemic dissociation in the blood. In this study, human serum-derived exosomes were employed to deliver colistin sulfate (ExoCol) against intracellular multidrug-resistant Escherichia coli associated with neonatal sepsis. Exosomes were isolated from a serum sample through the PEG precipitation method. Colistin sulfate (Col) was encapsulated within the exosomes and both the free exosomes (Exos) and colistin sulfate-loaded exosomes (ExoCol) were characterized using DLS, NTA, FTIR, ATR-FTIR, western blotting, Scanning Electron Microscopy (SEM), and UV-visible spectrophotometry. Macrophage RAW246.7 cells were treated with Exos and ExoCol, and confocal microscopy was done for the cellular uptake assay. Low to high concentrations of Exos (10-100 µg/mL), Col (0.5-6 µg/mL), and ExoCol (Exo: 100 µg/mL & 0.5-6 µg/mL)-treated macrophage cells were assessed to check cytotoxicity by MTT assay and intracellular drug release study by UV-visible spectrophotometry. The cells were then infected with multidrug-resistant Escherichia coli, and the same treatments were given to evaluate antibacterial efficacy by CFU count, intracellular live-dead bacterial imaging by confocal microscopy, and single-cell sorting by flow cytometry. After 24 h of the treatment, ExoCol-treated cells maintained higher cell viability (∼85-95%) than the free antibiotic-treated cells (60-80%), and ExoCol demonstrated significantly greater intracellular drug release (85-95%) as compared to free colistin sulfate (45-55%). Moreover, ExoCol eradicated more intracellular bacteria (4 log10 CFU/mL) than the free colistin sulfate (1 log10 CFU/mL). In conclusion, these findings imply that antibacterial therapy mediated by exosomes reduces cytotoxicity and increases bacterial eradication, with significant intracellular delivery. Therefore, ExoCol approaches as a promising nanotherapeutic for the treatment of neonatal sepsis. Future studies will involve in vivo models to further optimize doses and validate therapeutic efficacy and treatment strategies.

Keywords:  Colistin sulfate; Drug delivery; Exosome-encapsulated colistin sulfate; Exosomes; MDR E. coli; Macrophage RAW 264.7 cells; Neonatal sepsis

DOI:  https://doi.org/10.1016/j.ijpharm.2026.126870
Pharm Res. 2026 Apr 21.

Recent Progress in Exosome-Derived Nanocarriers for Breast Cancer Therapy: Advances, Translational Barriers, and Scale-Up Considerations.

Julie R Youssef, Esraa M Elgammal, Dina M Mahdy, Noha F Ghazi, George Bebawy.

  Breast cancer remains the most prevalent malignancy among women worldwide and a major cause of cancer-related mortality. Despite remarkable progress in molecularly targeted and immune-based therapies, therapeutic resistance, dose-limiting systemic toxicity, and inefficient drug delivery continue to hinder clinical outcomes, particularly in aggressive subtypes such as triple-negative breast cancer. Exosomes, naturally secreted nanosized vesicles, have emerged as a transformative platform owing to their biocompatibility, intrinsic targeting capability, and ability to transport diverse therapeutic cargos across biological barriers. Recent advances in exosome biology, engineering, and isolation technologies have reignited interest in their clinical exploitation as drug delivery systems. However, translation into clinical oncology remains in its early stages. This review provides a comprehensive overview of exosome-based drug delivery systems specifically within the context of breast cancer therapy, critically evaluating their sources, isolation techniques, cargo loading strategies, targeting mechanisms, and formulation considerations. It also examines preclinical findings demonstrating enhanced therapeutic efficacy and reduced off-target toxicity, alongside the limited yet growing number of clinical trials investigating exosome therapeutics in solid tumours. Importantly, the review identifies major gaps, including lack of standardized manufacturing protocols, incomplete pharmacokinetic understanding, and unresolved safety concerns, that currently impede clinical translation. By bridging molecular insights with translational perspectives, this work underscores the untapped potential of exosomes as next-generation drug carriers in breast cancer. It highlights the urgent need for harmonized methodologies, scalable production systems, and regulatory frameworks to enable their safe and effective integration into future cancer therapeutics.

Keywords:  breast cancer; drug delivery; exosomes; extracellular vesicles; phytochemical therapeutics; targeted therapy; translational nanomedicine

DOI:  https://doi.org/10.1007/s11095-026-04095-3
Biomed Mater. 2026 Apr 22.

Application of hybrid exosomes-mediated targeted delivery system for sinomenine hydrochloride in rheumatoid arthritis therapy.

Ziwei Feng, Yue Zhang, Liang Yao, Ruoqing Li, Chen Gu, Liangliang Gu, Guihua Zou, Lijing Yu, Yunna Chen, Sheng Zhang, Lei Wang, Xiaojie Mi, Weidong Chen.

  Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction, whose pathogenesis is closely associated with dysregulated macrophage polarization. Recent evidence highlights the inherent anti-inflammatory properties of exosomes derived from M2-macrophages (M2-Exo), positioning them as promising bioinspired vehicles for targeted delivery to inflammatory sites. Here, we present an innovative hybrid exosome system (SH@M2-Exo-Lip) for targeted RA therapy. This system was constructed via the fusion of sinomenine hydrochloride (SH)-loaded liposomes with M2-Exo, specifically designed to improve the drug loading capacity of exosomes and enhance the targeting efficacy of drug delivery systems. The results demonstrated that leveraging the innate targeting capability of M2-Exo, the SH@M2-Exo-Lip system achieved selective accumulation within inflamed joints in the collagen-induced arthritis (CIA) model, enabling precise SH release at pathological sites, and significantly reduced levels of pro-inflammatory cytokines and ameliorated arthritic symptoms. Furthermore, SH@M2-Exo-Lip efficiently scavenged the excess reactive oxygen species (ROS) and modulated the critical cGAS-STING innate immune pathway, thereby synergistically promoting the polarization of M1 macrophages towards the M2 phenotype, effectively ameliorating the joint microenvironment. Consequently, our study presents an innovative engineered hybrid exosome platform that offers a novel therapeutic strategy for RA treatment.

Keywords:  M2-exosomes; M2-macrophage; drug delivery; rheumatoid arthritis; sinomenine hydrochloride

DOI:  https://doi.org/10.1088/1748-605X/ae6383
J Nanobiotechnology. 2026 Apr 21.

Germ cell-directed exosomal delivery enables in vivo genetic modification in birds.

Hee Jung Choi, Kyung Min Jung, Yujin Han, Seung Je Woo, Jae Yong Han.

  Avian embryos present substantial barriers to early-stage genetic manipulation due to the rigid eggshell and opaque yolk, underscoring the need for alternative in vivo germline delivery systems. Extracellular vesicles (EVs), particularly exosomes, are biocompatible nanoscale carriers of nucleic acids, yet their potential for germline targeting in birds has not been investigated. Here, we isolated exosomes from long-term cultured chicken primordial germ cells (PGCs) and characterized their morphology, size distribution, and exosomal marker expression. PGC-derived exosomes efficiently delivered plasmid DNA into primary PGCs with minimal cytotoxicity. In vivo microinjection of plasmid-loaded exosomes into early chicken and quail embryos induced robust transgene expression within developing embryonic gonads, demonstrating their ability to traverse embryonic barriers and access germline niches. Vector-derived sequences persisted in embryonic and post-hatch gonads, and GFP-positive germ cells were detected in the testes of sexually mature G₀ quails, supporting preferential germline uptake and expression. Collectively, these findings establish PGC-derived exosomes as promising germline-directed nanocarriers for in vivo gene delivery in birds, with potential applications in avian genome engineering and germline modification.

Keywords:  Exosomes; Extracellular vesicles; Genetic modification; Germline targeting; Primordial germ cells

DOI:  https://doi.org/10.1186/s12951-026-04442-x
Eur J Pharm Sci. 2026 Apr 16. pii: S0928-0987(26)00106-5. [Epub ahead of print]221 107532

Engineered small extracellular vesicles provide low-dose salidroside delivery to attenuate retinal ganglion cell degeneration.

Xue-Ni Peng, Sheng-Jin Xiang, Yue-Xiao Wu, Jing Luo, Zai-Long Chi, Tong Li.

  Optic neuropathy is characterized by impaired optic nerve function resulting from various pathological processes, often leading to retinal ganglion cell (RGC) degeneration and irreversible vision loss. Several studies have demonstrated the neuroprotective effects of salidroside (Sal). However, its clinical application has been limited by the high dosage required and the short half-life of Sal. To enhance drug efficacy and prolong therapeutic effects, we developed engineered small extracellular vesicles (sEVs) loaded with Sal (sEVs-Sal) for intravitreal administration in a mouse model of optic nerve crush (ONC). Our findings demonstrate that sEV-mediated low-dose Sal administration significantly enhanced visual functional recovery in ONC mice by mitigating RGC degeneration and inhibiting microglial activation. Proteomic profiling indicated that sEVs-Sal concurrently modulate both the TNF-α/IL-1β inflammatory axis and the Caspase-3/Bcl-2 apoptotic pathway, thereby conferring dual anti-inflammatory and antiapoptotic effects. This study establishes an efficient sEV-based drug delivery platform and highlights the considerable therapeutic potential of sEVs-Sal in the treatment of optic nerve injury. By addressing the pharmacokinetic limitations of free Sal and augmenting neuroprotection, this nanoformulation represents a promising translational strategy for optic neuropathies.

Keywords:  Neuroprotection; Optic nerve injury; Retinal ganglion cells; Salidroside; Small extracellular vesicles

DOI:  https://doi.org/10.1016/j.ejps.2026.107532
J Nanobiotechnology. 2026 Apr 18.

Turmeric-derived exosome-coated ZIF-8 nanoplatform for targeted delivery of TGF-β1 siRNA in the treatment of liver fibrosis.

Yanyan Jiang, Xinliu Duan, Zitong Qi, Xuan Zhou, Wenjing Song, Li Jiang, Yawen Yu, Yueli Liu, Xu Chai, Xiaohu Tang, Xiaoyan He, Hangyu Xia, Qun Liu, Peng Zhang, Aiping Wang.

  Liver fibrosis constitutes a progressive pathological condition for which TGF-β1 pathway-targeted siRNA therapy holds considerable therapeutic potential. Nevertheless, clinical application of TGF-β1 siRNA is critically limited by inherent instability and inefficient delivery in vivo. In this study, we engineered an innovative siRNA delivery platform through the integration of turmeric-derived exosome-like nanovesicles (TDEs) with a metal-organic framework (ZIF-8) to generate TDEs@ZIF-8@TGFβ1siRNA nanoparticles, thereby enhancing siRNA delivery efficiency and therapeutic efficacy in liver fibrosis. Characterization revealed TDEs@ZIF-8@TGFβ1siRNA nanoparticles exhibited a well-defined nanostructure with a high TGF-β1 siRNA encapsulation efficiency of 64.73%. Additionally, the system exhibited pH-responsive release and lysosomal escape capabilities, significantly enhancing siRNA stability and cellular uptake efficiency. In vitro, TDEs@ZIF-8@TGFβ1siRNA effectively inhibited hepatic stellate cells (HSCs) activation, reducing TGF-β1, Collagen I, and CTGF mRNA levels by 78.6%, 72.1%, and 69.4%, respectively. In a CCl4-induced mouse model of liver fibrosis, TDEs@ZIF-8@TGFβ1siRNA treatment significantly improved hepatic function, reducing serum ALT and AST levels by 59.8% and 62.7%, respectively. Histological staining revealed a 71% reduction in fibrotic area, concomitant with marked downregulation of α-SMA and Collagen I expression by approximately 68% and 74%. Mechanistically, the therapeutic effects were mediated through TGF-β1 gene silencing and consequent inhibition of the TGF-β/Smad pathway, resulting in attenuated HSCs activation and diminished collagen deposition. These findings indicate that TDEs@ZIF-8@TGFβ1siRNA represents a promising biomimetic strategy for targeted gene therapy in liver fibrosis.

Keywords:  Liver fibrosis; TGF-β1 silencing; Turmeric-derived exosomes; ZIF-8; siRNA delivery

DOI:  https://doi.org/10.1186/s12951-026-04430-1
Bioact Mater. 2026 Sep;63 662-681

Intelligent plant exosomes synergize miRNAs and cisplatin for spatiotemporally precise multimodal treatment for TNBC with high safety.

Xi-Yuan Xu, Xuan Zhang, Yi-Yi Wang, Qi-Yao Xiao, Cheng Yang, De-Sheng Kong, Li-Hua Peng.

  Triple-negative breast cancer (TNBC) lacks common receptors and exhibits aggressive behavior, limiting treatment options due to drug resistance and systemic toxicity. TNBC chemotherapy is hindered by poor tumor targeting, drug resistance, and systemic toxicity. Herein, this study presented a cascade targeting exosomal-cisplatin synergistic microneedle nanoplatform (CDDP@RKTExo-MN) as an intelligent wearable therapeutic device for TNBC treatment. Medicinal plant Taxus chinensis derived exosomes (TExo), carrying therapeutic miRNA, was synergized with cisplatin that induced ER stress to trigger a multimodal anti-tumor effects. The cisplatin-loaded TExo was further modified with αvβ3 integrin peptides and an ER-targeting motif for tumor homing and precise subcellular delivery. Leveraging the superficial localization of TNBC, the engineered TExo was integrated into a 3D-printed microneedle patch to construct a closed-loop transdermal delivery system (CDDP@RKTExo-MN). This bioactive architecture ensures precise drug delivery at the tumor site, effectively maximizing therapeutic efficacy while circumventing the systemic off-target toxicity inherent to conventional delivery strategies. CDDP@RKTExo-MN was shown for the cascade targeting capabilities with both cancer cells and their endoplasmic reticulums. By coordinated regulation of MAPK and TNF pathways, the system generated synergistic effects in both significantly amplifying apoptotic signaling and activating immunological protection. In vivo studies conclusively validated its superior tumor suppression efficacy alongside a favorable biosafety.

Keywords:  Cisplatin; Plant exosome engineering; Transdermal-cascade targeting programmed delivery; Triple-negative breast cancer; Wearable microneedle patch

DOI:  https://doi.org/10.1016/j.bioactmat.2026.02.013
Mater Today Bio. 2026 Jun;38 103126

Microcarriers encapsulating COL1A1 mRNA-loaded nanovesicles for skin photoaging treatment.

Xiang Lin, Anne M Filppula, Luoran Shang, Hongbo Zhang, Dexuan Wang.

  Extracellular vesicles have shown great potential in treating ultraviolet (UV)-induced skin photoaging. However, effective delivery of these bioactive agents to achieve long-term therapeutic effects remains a significant challenge. In this study, we have developed recombinant human collagen (RHC)-based microcarriers loaded with native exosomes as well as Collagen type I alpha 1 chain (COL1A1) mRNA-encapsulating nanovesicles (Emvs) to treat skin photoaging. The microcarriers mitigated UV-induced cellular senescence in HaCaT cells, as evidenced by reduced oxidative stress, decreased apoptosis, and attenuation of senescence-associated markers. In the animal model, the microcarriers not only attenuated wrinkle formation, but also promoted type I collagen deposition in UV-damaged skin. These results together with the demonstrated biocompatibility highlight the potential of the microcarrier delivery system in photoaging treatment.

Keywords:  Microcarriers; Microfluidic electrospray; Nanovesicles; Photo-aging; mRNA delivery

DOI:  https://doi.org/10.1016/j.mtbio.2026.103126
Biomater Biosyst. 2026 Jun;22 100136

TeSe nanoparticle-integrated exosomes for accelerated diabetic Pressure ulcer healing via NIR-II triggered synergy.

Fangjia Li, Qiuyue Fang, Yi Zhang, Yimin Gong, Boxun Liu.

  Diabetic wounds, particularly combined with pressure ulcers, pose significant therapeutic challenges due to their complex pathophysiology. Conventional treatment strategies often fail to adequately address the multifactorial impairment of healing in these conditions. Here, we proposed and investigated a combinatory strategy employing human adipose-derived mesenchymal stem cell-derived exosomes (hADSC-Exos) with near-infrared-II (NIR-II)-responsive selenium telluride (TeSe) nanoparticle-mediated photothermal therapy (PTT). A full-thickness skin defect pressure ulcer model in diabetic mice was established to systematically evaluate different exosome administration regimens (single high-dose vs. multiple low-dose injections) and their combination effect with TeSe nanoparticle and NIR-II irradiation. We find that multiple low-dose subepidermal injections of hADSC-Exos resulted in more pronounced healing compared to a single high-dose strategy. The combination of low-dose exosomes with TeSe+NIR-II PTT markedly enhanced wound closure quality and stimulated hair follicle regeneration within 21 days. In vitro, TeSe nanoparticles demonstrated effective NIR-II photothermal conversion and antibacterial activity. Their integration with exosomes significantly boosted fibroblast migration and proliferation. Histological analysis confirmed that the combined therapy potently promoted angiogenesis (increased CD31 expression), reduced inflammation (decreased CD68 expression), and improved collagen remodeling (lowered collagen I/III ratio). This work presents an innovative therapeutic approach that synergizes bioactive exosome delivery with microenvironment modulation via antibacterial photothermal therapy, offering a promising prospective treatment for diabetic pressure ulcers.

Keywords:  Anti-microbial; Photothermal therapy; TeSe nanomaterial; Wound healing; hADSC-Exos

DOI:  https://doi.org/10.1016/j.bbiosy.2026.100136