bims-engexo 2026-09-13 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2026–09–13
twelve papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Engineering extracellular vesicles for targeted siRNA delivery: Advances, therapeutic applications, and clinical translation.
Engineering exosomes in the treatment of sensorineural hearing loss: from basic research to clinical applications.
Vectors Trgeting Hepatocyte: Reconstructive Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes.
Resveratrol-loaded human dental pulp stem cell-derived exosomes enhance the efficacy of blue LED-mediated antimicrobial photodynamic therapy against mature cariogenic biofilms.
Surface-engineered milk-derived extracellular vesicles enable oral miRNA therapy against immunosuppressive pancreatic cancer.
Exosome-Based Drug Delivery: Prospects in Regenerative Medicine and Cancer.
Targeting m6A writer METTL3 with engineered nanovesicles reduces neuroinflammation in vitro and in vivo.
Extracellular vesicles for next-gen therapeutics and drug delivery.
Exosome-Based Drug Delivery Systems in Colorectal Cancer: Current Evidence and Future Perspectives.
A ROS-responsive platelet extracellular vesicle biomimetic nanosystem regulates CD36/Fyn-CXCL-NETosis pathway-mediated immune-inflammatory amplification in the treatment of transfusion-related acute lung injury.
A universally conserved OMV-YidR conjugate nanovaccine confers broad protection against hypervirulent and carbapenem-resistant Klebsiella pneumoniae.
Preparation of oxygen-filled adipose-derived stem cells exosome-nanobubbles gel for ultrasound-assisted full-thickness wound healing in rats.

Nanomedicine. 2026 Sep 05. pii: S1549-9634(26)00121-8. [Epub ahead of print]77 103020

Engineering extracellular vesicles for targeted siRNA delivery: Advances, therapeutic applications, and clinical translation.

G S Amrish Varshan, S Karthick Raja Namasivayam.

  Small interfering RNA (siRNA) therapeutics have emerged as a transformative approach for sequence-specific gene silencing, offering the potential to treat a broad spectrum of diseases by selectively suppressing disease-associated genes. However, the clinical translation of siRNA remains limited by rapid enzymatic degradation, poor cellular uptake, inadequate endosomal escape, and off-target effects, necessitating the development of efficient delivery systems. Extracellular vesicles (EVs) have gained considerable attention as natural nanocarriers owing to their excellent biocompatibility, low immunogenicity, intrinsic targeting capability, and ability to protect therapeutic cargo while traversing complex biological barriers. This review comprehensively discusses the biological characteristics of EVs, the molecular basis of RNA interference, and the major challenges associated with siRNA delivery [Fig. 1]. Recent advances in EV engineering, including cargo-loading strategies such as electroporation, sonication, extrusion, parent-cell engineering, and microfluidic approaches, together with surface functionalization using peptides, antibodies, aptamers, and hybrid nanoplatforms, are critically evaluated for improving targeting specificity and intracellular delivery. Furthermore, the therapeutic applications of engineered EV-mediated siRNA delivery in cancer, neurological disorders, liver diseases, cardiovascular diseases, inflammatory disorders, and infectious diseases are systematically summarized, highlighting their potential to enhance gene silencing while minimizing systemic toxicity. Current challenges related to large-scale manufacturing, cargo-loading efficiency, standardization, quality control, regulatory approval, and clinical translation are also discussed, together with emerging technologies involving synthetic biology, genome engineering, artificial intelligence, and multifunctional hybrid vesicles. Overall, engineered extracellular vesicles represent a highly versatile and biologically inspired platform for targeted siRNA delivery, providing a promising foundation for the development of next-generation precision RNA therapeutics and accelerating the clinical translation of gene-silencing strategies.

Keywords:  Extracellular vesicle engineering; Extracellular vesicles; Gene silencing; Small interfering RNA

DOI:  https://doi.org/10.1016/j.nano.2026.103020
Front Mol Neurosci. 2026 ;19 1886218

Engineering exosomes in the treatment of sensorineural hearing loss: from basic research to clinical applications.

Siqi Wang, Juanjuan Li, Bingxing Yang, Mengdi Li, Man Yu, Peng Zhang, Suwen Bai, Xianhai Zeng.

  Engineered exosomes demonstrate good biocompatibility, barrier-crossing ability, and programmable drug-loading capacity. Recently, they have steadily emerged as a promising area of study for precision intervention in sensorineural hearing loss. This review focuses on numerous main topics, including the selection of exosome sources and donor-cell pretreatment techniques, surface targeting strategies, therapeutic cargo loading methods, the mechanisms by which exosomes cross the blood-labyrinth barrier, and recent advancements in research on the role of exosomes in hair cell protection, spiral ganglion neuron protection, supporting-cell plasticity, and cochlear microenvironment remodeling. This review also examines the key challenges in the clinical translation of exosomes. It comprehensively reviews direct cochlear exosome evidence for hair cell protection and auditory protection, separating these results from indirect non-cochlear exosome evidence and theoretical engineering approaches for spiral ganglion neuron protection, supporting-cell-mediated regeneration-related mechanisms, and cochlear neurovascular microenvironment remodeling. In addition to outlining a framework that combines targeted delivery and functional regulation for sensorineural hearing loss, this review highlights the hearing-protective potential of engineered exosomes in preclinical models and requires further experimental validation. Despite the positive outlook, there are still notable issues with the durability of therapeutic effects, mechanistic clarity, and clinical translatability. Future studies should prioritize standardization of extracellular vesicle reporting, dose reproducibility, clinically relevant models, and long-term functional outcomes.

Keywords:  blood-labyrinth barrier; cochlear microenvironment; engineered exosomes; sensorineural hearing loss; targeted drug delivery

DOI:  https://doi.org/10.3389/fnmol.2026.1886218
Tissue Eng Regen Med. 2026 Sep 11.

Vectors Trgeting Hepatocyte: Reconstructive Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes.

Yan-Feng Yin, Chun-Tao Yan, Zheng Guan, Lu Yu, Chun-Mei Lei, Dongdong Wang, Jiayin Yang.

   BACKGROUND: Specific binding of the hepatitis B virus (HBV) pre-S1 protein to Na+/taurocholate Cotransporting Polypeptide (NTCP) on the surface of hepatocytes mediates viral entry into host cells. Exosomes, which serve as natural delivery vehicles, can protect their cargo from degradation in the extracellular environment.
METHODS: Umbilical cord mesenchymal stem cell (UC-MSC)-derived exosomes were isolated and characterized. The gene sequence encoding the CD90 C-terminal signal peptide was fused with the pre-S1 gene and cloned into a lentiviral vector (VP045-U6-PGK-preS1-CD90-hygro), enabling membrane anchoring of pre-S1 on UC-MSC-derived exosomes. PKH26 probe, Phalloidin-AF488 probe, and DiR dye were used to explore the targeting of reconstituted UC-MSC-derived exosomes on hepatocytes and liver.
RESULTS: Isolated UC-MSCs exhibited fibroblast-like morphology and retained the capacity to differentiate into osteoblasts, adipocytes, and chondrocyte. The immunophenotype of UC-MSCs was characterized as CD34-CD45-CD44+CD73+CD90+CD105+Oct-4+. UC-MSC-derived exosomes exhibited a cup-shaped bilayer structure, with a diameter of 78.47 ± 13.46 nm and a concentration of 1.28 × 1010 particles/mL. The VP045-U6-PGK-preS1-CD90-hygro lentivirus successfully mediated pre-S1 expression on the membranes of UC-MSC-derived exosomes. In vitro, hepatocytes (HepG2.2.15 and HepaRG cells) internalized significantly greater amounts of reconstituted UC-MSC-derived exosomes than native exosomes, with the effect being particularly pronounced in HepG2.2.15 cells. No significant difference was observed in lung cells. In vivo, reconstituted UC-MSC-derived exosomes were predominantly accumulated in the liver of BALB/c mice, whereas minimal signals were detected in the lung, spleen and kidney.
CONCLUSION: UC-MSC-derived exosomes expressing pre-S1 exhibit specific tropism for hepatocytes and liver tissue. These engineered exosomes represent a promising delivery platform for therapeutic drugs and nucleic acid cargos in HBV-targeted therapy.

Keywords:  Delivery; Exosome; Extracellular vesicles; Hepatitis B Virus; Hepatocyte; Liver; Umbilical cord mesenchymal stem cells

DOI:  https://doi.org/10.1007/s13770-026-00826-0
Lasers Med Sci. 2026 Sep 11. pii: 223. [Epub ahead of print]41(1):

Resveratrol-loaded human dental pulp stem cell-derived exosomes enhance the efficacy of blue LED-mediated antimicrobial photodynamic therapy against mature cariogenic biofilms.

Maryam Pourhajibagher, Abbas Bahador.

  Antimicrobial photodynamic therapy (aPDT) is a promising adjunctive approach for biofilm-associated oral diseases, though the poor stability and bioavailability of natural photosensitizers remain limiting factors. This study evaluated the anti-biofilm efficacy of resveratrol-loaded human dental pulp stem cell-derived exosomes (Res@hDPSC-Exos) activated by blue LED irradiation against mature cariogenic biofilms. hDPSC-Exos were isolated, characterized, and loaded with resveratrol; physicochemical properties, encapsulation efficiency, and exosomal integrity were assessed by TEM, DLS, and CD63 expression. Mature Streptococcus mutans and Lactobacillus acidophilus biofilms were established on human enamel specimens. The minimum biofilm reduction concentration (MBRC) of Res@hDPSC-Exos and minimum biofilm reduction dose (MBRD) of blue LED were determined, and biofilms were treated according to six groups: untreated control, free resveratrol, empty hDPSC-Exos, blue LED alone, and Res@hDPSC-Exos-mediated aPDT at 1/2× and 1/4×MBRC. Biofilm biomass, metabolic activity, and gtfB/slpA virulence gene expression were assessed by crystal violet staining, XTT assay, and qRT-PCR, respectively. Resveratrol was successfully encapsulated into hDPSC-Exos (encapsulation efficiency ≈ 63%) without compromising vesicle morphology or membrane integrity. The MBRC of Res@hDPSC-Exos was 250 µg/mL for S. mutans and 125 µg/mL for L. acidophilus, and the MBRD of blue LED was 300 s for both species. Free resveratrol, empty hDPSC-Exos, and blue LED alone produced only modest, non-significant effects (≈ 5-15%, P > 0.05). In contrast, Res@hDPSC-Exos-mediated aPDT at 1/2×MBRC with sub-MBRD irradiation (240 s) significantly reduced biofilm biomass (84.7% and 75.2%) and metabolic activity (88.9% and 85.0%) in S. mutans and L. acidophilus, respectively (P < 0.001), and downregulated gtfB and slpA expression to 0.15-fold and 0.19-fold of controls (P < 0.001). Res@hDPSC-Exos-mediated aPDT effectively suppressed biofilm growth, metabolic activity, and virulence gene expression in mature cariogenic biofilms under conservative irradiation conditions. Given the minimal activity of the individual components relative to the combined treatment, exosome-assisted delivery may contribute to enhancing the photodynamic performance of resveratrol; however, as this study did not directly compare free resveratrol- and exosome-mediated aPDT under identical conditions, this interpretation should be regarded as preliminary. Further in vivo, clinical, and comparative studies are warranted to confirm its translational potential.

Keywords:   Lactobacillus acidophilus ; Streptococcus mutans ; Antimicrobial photodynamic therapy; Dental caries; Exosomes; Human dental pulp stem cells; Resveratrol

DOI:  https://doi.org/10.1007/s10103-026-05024-x
Mater Today Bio. 2026 Oct;40 103600

Surface-engineered milk-derived extracellular vesicles enable oral miRNA therapy against immunosuppressive pancreatic cancer.

Youngri Ryu, Hochung Jang, Eun Hye Kim, Junha Lee, Byeongmin Park, Yewon Cho, Wonjun Kim, Hong-Yeol Yoon, Sun Hwa Kim, Dae-Hyuk Kweon, Man Kyu Shim, Yoosoo Yang.

  Pancreatic ductal adenocarcinoma (PDAC) shows limited responsiveness to conventional therapies due to an immunosuppressive tumor microenvironment (TME) characterized by programmed death-ligand 1 (PD-L1)-mediated immune escape and oncogenic microRNA-21 (miR-21) signaling. Despite the potential of miRNA therapeutics, their clinical translation is hindered by the lack of stable, non-invasive delivery systems capable of bypassing complex biological barriers. Here, we develop a scalable biogenic delivery platform based on surface-engineered milk-derived extracellular vesicles (MEVs) for systemic transport of anti-miR-21 (α21) after oral administration. MEVs were isolated using a reproducible purification workflow and functionalized with a PD-L1-binding peptide (PBP) to facilitate tumor-associated uptake while preserving vesicle integrity and colloidal stability. The engineered vesicles (α21@MEVPBP) remained stable under simulated gastrointestinal conditions, underwent efficient transepithelial transport, and exhibited selective accumulation in PD-L1high pancreatic tumors in vivo, demonstrating a gut-to-tumor delivery pathway. Following cellular internalization, α21 delivery restored tumor-suppressive signaling and induced endoplasmic reticulum stress-associated immunogenic cell death (ICD). Concurrently, modulation of tumor-associated macrophages toward a pro-inflammatory phenotype enhanced CD8+ T cell activation and antitumor immune responses, leading to significant tumor growth inhibition without detectable systemic toxicity. These findings establish α21@MEVPBP as an orally deliverable nanoplatform that bridges biogenic material engineering with targeted immune modulation. Together, the results demonstrate that surface engineering of naturally derived vesicles enables controlled systemic RNA transport via an oral administration route and provides a generalizable strategy for non-invasive delivery of nucleic acid therapeutics to solid tumors.

Keywords:  Cancer immunotherapy; MicroRNA-21; Milk-derived extracellular vesicle; Oral drug delivery; Pancreatic ductal adenocarcinoma

DOI:  https://doi.org/10.1016/j.mtbio.2026.103600
Pharm Nanotechnol. 2026 Sep 08.

Exosome-Based Drug Delivery: Prospects in Regenerative Medicine and Cancer.

Pratik Rajale, Nilesh Meshram, Shreya Kalbandhe, Kuldeep Vinchurkar, Laxmikant Borse.

  Various cell types produce small extracellular vesicles called exosomes, which are becoming more and more popular as natural delivery systems for medicinal compounds in cancer treatment and regenerative medicine. They are ideal drug delivery vehicles because they are stable, have minimal immunogenicity, and can transport a variety of molecules, including proteins, nucleic acids, and small drugs, across biological barriers. Recent developments in bioengineering have produced "designer exosomes" with enhanced cargo-loading efficiency, superior targeting, and surface features that can be altered. To overcome these issues like poor biodistribution and low drug capacity, exosomes can also be mixed with other nanocarriers, such as liposomes and polymeric nanoparticles. Clinical trials investigating applications in cardiovascular repair, neurological disorders, and targeted oncology are now underway. Exosome-based therapeutics exhibit promise in tissue regeneration and cancer therapy. Large-scale manufacturing, standardization of isolation techniques, regulatory approval, and long-term safety are still obstacles, nevertheless. Future studies will concentrate on creating customized treatments that meet precision medicine objectives, as well as building multifunctional and hybrid exosomes. Exosomes have the potential to become next-generation delivery systems that revolutionize cancer therapy and regenerative medicine treatment approaches with further development.

Keywords:  Exosomes; cancer therapy; clinical translation; drug delivery; nanocarriers; regenerative medicine

DOI:  https://doi.org/10.2174/0122117385453242260607095639
Nat Commun. 2026 Aug 08. pii: 9534. [Epub ahead of print]17(1):

Targeting m6A writer METTL3 with engineered nanovesicles reduces neuroinflammation in vitro and in vivo.

Liangfu Xu, Yuanwei Pan, Guanjun Li, Peng She, Qian-Fang Meng, Zhigang Liu, Lang Rao.

Epigenetic editing, particularly N6-methyladenosine (m6A) modification, represents a promising therapeutic strategy by silencing genes without altering DNA sequence. However, in vivo epigenetic intervention of neuroinflammation remains challenging and has rarely been explored. Here we developed a hybrid epigenetic nanomodulator, siMETTL3-hNVs, by integrating natural microglia-derived nanovesicles (NVs) with synthetic liposomes pre-loading small interfering RNA targeting the m6A writer methyltransferase-like 3 (METTL3). Natural NVs enabled siMETTL3-hNVs to achieve inflamed-brain delivery through CCR2-CCL2 chemotaxis and caveolae-mediated transcytosis across the blood-brain barrier. More importantly, relying on abundant cytokine receptors on the NVs, siMETTL3-hNVs served as decoys to neutralize pro-inflammatory cytokines, synergizing with the intracellular silencing of METTL3 to drive microglial M2 repolarization. In female mouse models of acute neuroinflammation and radiation-induced brain injury, siMETTL3-hNVs treatment significantly reduced cytokine levels, attenuated hippocampal damage, and ameliorated cognitive deficits. This work overcomes critical delivery bottlenecks in m6A-based therapeutics and establishes a robust strategy for epigenetic reprogramming of neuroinflammation.

DOI: https://doi.org/10.1038/s41467-026-75862-4
Mol Biomed. 2026 Sep 09. pii: 166. [Epub ahead of print]7(1):

Extracellular vesicles for next-gen therapeutics and drug delivery.

Nawaz Khan, Zeynab Ahmadova, Yujie Shi, Tayyab Shafiq, Yujie Liang, Li Duan.

  Extracellular vesicles (EVs) are membrane-bound, nano-sized particles released by diverse cell types. They serve as key mediators of intercellular communication by transporting a broad repertoire of proteins, lipids, nucleic acids, and metabolites to recipient cells within a protective lipid bilayer. Owing to their natural origin, intrinsic stability, low immunogenicity, and ability to cross biological barriers, EVs are highly attractive candidates for next-generation therapeutics and drug delivery platforms. In this review, we summarize the biology of EVs and highlight the features critical for their application in therapeutic delivery. We trace their multiple origins, ranging from mammalian and plant cells to bacteria, underscoring their ubiquity across biological systems. We then analyze the advantages of EVs as next-generation delivery vehicles. From a practical standpoint, we examine current strategies for EV isolation, purification, characterization, and engineering. Importantly, we showcase several therapeutic applications of EVs for intractable diseases that are refractory to conventional approaches, such as cancer and immune disorders. We also discuss the major challenges on the path to clinical translation, particularly scalable and standardized production, as well as safety and immunogenicity. To fully realize the clinical potential of EV-based therapies, future research should prioritize the development of robust manufacturing protocols and comprehensive safety evaluations.

Keywords:  Drug delivery; Exosomes; Extracellular vesicles; Immunotherapy; Vaccine

DOI:  https://doi.org/10.1186/s43556-026-00571-9
AAPS J. 2026 Sep 08. pii: 134. [Epub ahead of print]28(5):

Exosome-Based Drug Delivery Systems in Colorectal Cancer: Current Evidence and Future Perspectives.

Lucas Henrique Domingos da Silva, Juliana Ferreira Floriano, Marlus Chorilli.

  Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide, being the third most frequently diagnosed cancer and the second leading cause of death. Due to the high incidence of CRC cases, its biological complexity, and high morbidity and mortality, the development of more effective and less aggressive therapeutic approaches is an urgent need. Extracellular vesicles (EVs), especially EXs, are a very viable alternative as a nanocarrier for anticancer molecules for the treatment of CRC, as EXs are biologically relevant EVs with considerable therapeutic potential. EXs are nanoscale vesicles approximately 30-200 nm in diameter, identical in composition to the membrane of their parent cells, and carry a bioactive cargo of proteins, lipids, nucleic acids, and glycoconjugates. Beyond their physiological functions, EXs are gaining prominence as next-generation drug delivery platforms. Their ability to improve the efficacy of antitumor therapies, potentially reducing adverse effects associated with conventional chemotherapy and radiotherapy, makes them very promising. Furthermore, functionalizing the surface with targeting ligands, such as MUC1 aptamers, AS1411, or iRGD peptides, can further increase its specificity for CRC cells. Advances in drug delivery techniques, including passive incubation, electroporation, and chemical modification, have enabled the incorporation of conventional chemotherapeutic agents such as doxorubicin, 5-fluorouracil, and SN-38, as well as nucleic acid-based therapies, including microRNA and siRNA. Due to the limitations and invasive nature of current treatments for CRC, new studies to obtain innovative and targeted therapeutic strategies are essential to reduce harmful effects. Therefore, exosome-based drug delivery systems represent a promising and clinically relevant avenue for future cancer therapy.

Keywords:  anticancer therapy; cancer colorectal; drug-delivery; exosomes; extracellular vesicles

DOI:  https://doi.org/10.1208/s12248-026-01301-3
Redox Biol. 2026 Sep 06. pii: S2213-2317(26)00374-5. [Epub ahead of print]97 104375

A ROS-responsive platelet extracellular vesicle biomimetic nanosystem regulates CD36/Fyn-CXCL-NETosis pathway-mediated immune-inflammatory amplification in the treatment of transfusion-related acute lung injury.

Jiani Gao, Ke Zhou, Yijiu Ren, Fengjing Yang, Minjue Shan, Yubing Fang, Changbo Sun, Weili Han, Chang Chen, Xuefei Hu.

  Transfusion-related acute lung injury (TRALI) remains a life-threatening complication of blood transfusion, yet the macrophage-neutrophil-NETosis inflammatory amplification mechanism and effective interventions are still incompletely defined. Here, we examined a CD36/Fyn-CXCL-related axis in TRALI and evaluated a ROS-responsive platelet extracellular vesicle biomimetic nanosystem (PEV@SP@EG) as a targeted delivery strategy. In a murine TRALI model, exploratory single-cell transcriptomic analysis showed immune-cell remodeling and linked CD36 expression to M1-like macrophage features. CD36 knockdown or pharmacological inhibition of Fyn/NF-kappaB reduced M1 polarization markers, CXCL production, and ROS generation. Conditioned medium from CD36-overexpressing BMDMs promoted neutrophil migration and NETosis, whereas CXCL-CXCR2 blockade or CD36/Fyn inhibition weakened these responses. PEV@SP@EG showed ROS-triggered drug release and preferential lung enrichment. In vivo, PEV@SP@EG attenuated CD36/Fyn-NF-kappaB-CXCL-related inflammatory signaling, NET formation, and oxidative stress in TRALI lung tissue, with concomitant improvement in lung architecture and gas exchange. These findings support a role for macrophage CD36/Fyn signaling in TRALI-associated macrophage-neutrophil inflammatory crosstalk and suggest that PEV@SP@EG may provide a targeted nanotherapeutic delivery platform for TRALI intervention.

Keywords:  Biomimetic nanosystem; CD36/Fyn signaling axis; Immune-inflammatory amplification; Neutrophil extracellular trap-osis; Single-cell RNA sequencing; Transfusion-related acute lung injury

DOI:  https://doi.org/10.1016/j.redox.2026.104375
Emerg Microbes Infect. 2026 Sep 07. 2731500

A universally conserved OMV-YidR conjugate nanovaccine confers broad protection against hypervirulent and carbapenem-resistant Klebsiella pneumoniae.

Shuangjun He, Yang Zhang, Ahui Song, Chenyu Fan, Feng Zhao, Wei Zhou, Cuiying Xie, Chu Guo, Shengliang Chen, Yi Chen.

  The escalating crisis of multi-drug resistant (MDR) Klebsiella pneumoniae (KP) renders standard antibiotic treatments increasingly ineffective, necessitating a shift toward alternative approaches like vaccination. However, the development of a broadly protective vaccine remains hindered by the pathogen's extensive serotype diversity. To overcome this limitation, we targeted YidR-a highly conserved protein with potential as a universal antigen-and engineered a semi-synthetic conjugate vaccine by covalently linking it to KP-derived outer membrane vesicles (OMVs). The OMV-YidR conjugate successfully overcame the poor intrinsic immunogenicity of soluble YidR, eliciting robust antigen-specific IgG titers >20,000-fold higher than the unconjugated protein. Furthermore, the conjugate vaccine drove a shift from a weak Th2 bias to a potent, protective Th1/Th17 cellular profile. Crucially, this enhanced immunogenicity translated into broad-spectrum efficacy: while unconjugated OMVs protected only against the homologous strain, the OMV-YidR conjugate conferred complete (100%) survival against lethal challenges with diverse clinical isolates, including hypervirulent and carbapenem-resistant lineages. Mechanistic and comparative analyses revealed that covalent linkage-rather than simple physical co-administration-was essential for this superior efficacy, which was correlated with the preferential trafficking and uptake of the antigen by B cells in the draining lymph nodes. These findings establish the OMV-YidR conjugate as a highly potent, universal vaccine candidate capable of bypassing serotype limitations to prevent untreatable MDR K. pneumoniae infections.

Keywords:  Klebsiella pneumoniae; YidR protein; antibiotic resistance; nanovaccine; outer membrane vesicle

DOI:  https://doi.org/10.1080/22221751.2026.2731500
Biomed Pharmacother. 2026 Sep 05. pii: S0753-3322(26)00940-6. [Epub ahead of print]203 119904

Preparation of oxygen-filled adipose-derived stem cells exosome-nanobubbles gel for ultrasound-assisted full-thickness wound healing in rats.

Elnaz Bagheri, Elahehsadat Aminyazdi, Sara Amel, Mohammad Ramezani, Khalil Abnous, Seyed Mohammad Taghdisi, Mona Alibolandi.

  Effective wound healing is often hindered by hypoxia, inflammation, and impaired angiogenesis. Although mesenchymal stem cell (MSC)-based therapies have shown potential, their clinical application remains limited. As a result, MSC-derived exosomes, particularly adipose-derived stem cell exosomes (ADSC-Exos), have been proposed as a cell-free alternative; however, they still face limitations, including suboptimal efficiency in targeted delivery. To address these critical obstacles in existing regenerative therapies, we isolated ADSC-Exos from adipose tissue and fabricated a novel ultrasound-responsive, carbomer-based hydrogel incorporating oxygen-enriched ADSC-Exo nanobubbles (Gel-Exo-NB+US). The preclinical wound-healing potential of the developed nanohydrogel was evaluated using a full-thickness wound model in Wistar rats. The engineered hydrogel exhibited favorable physicochemical properties, including shear-thinning and thixotropic behavior, enabling efficient topical application and enhanced tissue adhesion. In a rat full-thickness skin defect model, the combined Gel-Exo-NB and Gel-Exo-NB + US treatments achieved the highest wound-closure rate among all groups, with enhanced re-epithelialization, a reduced scar index, elevated CD31 and α-SMA expression, increased fibroblast proliferation, and increased blood vessel formation. Furthermore, unprecedented hair-follicle regeneration and abundant collagen deposition were observed in the Gel-Exo-NB + US-treated group compared with the Gel-Exo-NB-treated group, highlighting the pivotal role of ultrasound in skin defect regeneration. Notably, the resulting collagen deposition, abundant hair follicles, and thin epidermis suggest potential for scarless wound healing. These therapeutic outcomes are attributed to the synergistic effects of simultaneous ultrasound-mediated exosome therapy and oxygen delivery.

Keywords:  Adipose-derived stem cell; Exosome; Hydrogel; Nanobubble; Wound healing; ultrasound

DOI:  https://doi.org/10.1016/j.biopha.2026.119904