bims-engexo 2025-06-15 papers

bims-engexo

Biomed News

on Engineered exosomes

Issue of 2025–06–15
seven papers selected by
Ravindran Jaganathan, Universiti Kuala Lumpur

Exosomes in cancer nanomedicine: biotechnological advancements and innovations.
Engineered exosomal miR140 modulates mitophagy of chondrocytes through targeting CAPN1 to alleviate osteoarthritis.
Engineered RVG-exosomes-mediated delivery of siRNAs targeting NMDAR alleviates orofacial neuropathic pain by suppressing central sensitivity.
Exosomes in inflammation and cancer: from bench to bedside applications.
Theranostics exosomes as autophagy mediators in cancer: Recent trends and advances.
Research progress on exosomes from different sources in osteoarthritis and cartilage injury.
ADSC exosomes improve high glucose induced fibroblast oxidative stress injury and accelerate DFU wound healing via regulating Keap1/Nrf2 axis.

Mol Cancer. 2025 Jun 07. 24(1): 166

Exosomes in cancer nanomedicine: biotechnological advancements and innovations.

Jacky J J Liu, Duanrui Liu, Sally K Y To, Alice S T Wong.

  Exosomes, as natural intercellular messengers, are gaining prominence as delivery vehicles in nanomedicine, offering a superior alternative to conventional synthetic nanoparticles for cancer therapeutics. Unlike lipid, polymer, or metallic nanoparticles, which often face challenges related to immunogenicity, targeting precision, and off-tumor toxicity, exosomes can effectively encapsulate a diverse range of therapeutic agents while exhibiting low toxicity, favorable pharmacokinetics, and organotropic properties. This review examines recent advancements in exosome bioengineering over the past decade. Innovations such as microfluidics-based platforms, nanoporation, fusogenic hybrids, and genetic engineering have significantly improved loading efficiencies, production scalability, and pharmacokinetics of exosomes. These advancements facilitate tumor-specific cargo delivery, resulting in substantial improvements in retention and efficacy essential for clinical success. Moreover, enhanced biodistribution, targeting, and bioavailability-through strategies such as cell selection, surface modifications, membrane composition alterations, and biomaterial integration-suggests a promising future for exosomes as an ideal nanomedicine delivery platform. We also highlight the translational impact of these strategies through emerging clinical trials. Additionally, we outline a framework for clinical translation that focuses on: cargo selection, organotropic cell sourcing, precision loading methodologies, and route-specific delivery optimization. In summary, this review emphasizes the potential of exosomes to overcome the pharmacokinetic and safety challenges that have long impeded oncology drug development, thus enabling safer and more effective cancer treatments.

Keywords:  Cancer; Drug delivery; Engineered exosomes; Extracellular vesicles; Nanomedicine

DOI:  https://doi.org/10.1186/s12943-025-02372-0
Sci China Life Sci. 2025 Jun 10.

Engineered exosomal miR140 modulates mitophagy of chondrocytes through targeting CAPN1 to alleviate osteoarthritis.

Yuan Liu, Kai Huang, Sheng-Liang Zhou, Shuai Li, Hai-Bo Si, Yi Zeng, Hui-Qi Xie, Bin Shen.

  Osteoarthritis (OA) is a prevalent degenerative disease involving mitophagy dysfunction of chondrocytes. As OA progresses, miR140 expression in chondrocytes decreases, and its therapeutic potential has shown protective effects. However, the variation in mitophagy across different stages of OA in human chondrocytes, as well as the role of miR140 in modulating mitophagy, have remained insufficiently elucidated. In this study, we observed that mitochondrial morphology deteriorates with OA progression, from mild swelling in the early stage of OA (E-OA) to disrupted cristae in the mid-to-late stage of OA (ML-OA). Mitophagy levels were mildly elevated in E-OA chondrocytes compared with normal controls, whilst ML-OA chondrocytes exhibited significantly reduced and impaired mitophagy. Notably, miR140 was found to down-regulate CAPN1, an intracellular cysteine protease affecting mitochondrial and lysosomal membranes. Targeting the miR140/CAPN1 axis was revealed to improve mitochondrial morphology, decrease reactive oxygen species (ROS) accumulation, and promote mitophagy in chondrocytes. To further overcome the inherent instability and limited bioavailability of miR140 when administered directly, engineered exosomes overexpressing miR140 derived from human urine-derived stem cells (hUSCs-140-Exos) were constructed. In vitro, hUSCs-140-Exos were demonstrated to promote mitophagy and preserve mitochondrial function. Moreover, intra-articular injection of hUSCs-140-Exos in vivo effectively delivered miR140 to OA chondrocytes, resulting in improved gait, restoration of subchondral bone structure, and mitigation of OA progression. Overall, this study provides a novel and promising strategy for OA treatment, demonstrating significant therapeutic potential.

Keywords:  CAPN1; exosomes; human urine-derived stem cells; miR140; mitophagy; osteoarthritis

DOI:  https://doi.org/10.1007/s11427-024-2843-7
J Pain. 2025 Jun 05. pii: S1526-5900(25)00684-4. [Epub ahead of print]33 105457

Engineered RVG-exosomes-mediated delivery of siRNAs targeting NMDAR alleviates orofacial neuropathic pain by suppressing central sensitivity.

Yan-Yan Zhang, Yue-Ling Li, Qin-Xuan Song, Ya-Ting Yi, Yu-Heng Feng, Yi-Ke Li, Cheng Zhou, Chun-Jie Li, Fei Liu, Jie-Fei Shen.

  Orofacial neuropathic pain (NP) is a common complication in oral clinical practice that severely affects quality of life. However, NP does not currently receive effective medications. Engineered exosomes have great potential as drug delivery systems for treating diseases. Here, patch clamp techniques showed that the deficiency of N-methyl-D-aspartic acid receptor (NMDAR) subunits 2A and 2B reversed the spontaneous excitatory postsynaptic current (sEPSC) frequency and neuronal excitability in the spinal trigeminal nucleus caudalis (SpVc) after injury, which is an effective therapeutic target for NP. Hence, we successfully employed exosomes (EXOs) modified with the nervous system-specific rabies virus glycoprotein (RVG) peptide, which exhibited excellent targeting ability towards N2a-Neuro cells and SpVc tissue. RVG-EXOs loaded with siRNAs of NR2A/B efficiently targeted SpVc neurons, further reducing neuronal excitability and relieving the orofacial NP. Taken together, our study investigated the role of NR2A/B in central nociceptive sensitization and suggested that RVG-EXOs-mediated delivery of siRNAs targeting NR2A and NR2B was effective for orofacial NP treatment. PERSPECTIVE: This study investigated the crucial role of NMDAR in central sensitization of the SpVc after nerve injury. In this study, we innovatively explored a central targeted drug delivery system based on engineered RVG-EXOs, providing a basis for targeted minimally invasive treatments of orofacial NP.

Keywords:  Central sensitization; Drug delivery; Engineered RVG-exosomes; NMDAR; Orofacial neuropathic pain

DOI:  https://doi.org/10.1016/j.jpain.2025.105457
Mol Biomed. 2025 Jun 10. 6(1): 41

Exosomes in inflammation and cancer: from bench to bedside applications.

Shiyuan Huang, Fang Yan, Yi Qiu, Tao Liu, Wenjin Zhang, Yige Yang, Rao Zhong, Yang Yang, Xi Peng.

  Exosomes, lipid bilayer nanovesicles secreted by nearly all cell types, play pivotal roles in intercellular communication by transferring proteins, nucleic acids, and lipids. This review comprehensively summarizes their multiple functions in inflammation and cancer. In inflammation, exosomes exhibit context-dependent pro- or anti-inflammatory effects: they promote acute responses by delivering cytokines and miRNAs to activate immune cells, yet suppress chronic inflammation via immunoregulatory molecules. Two representative inflammatory diseases, namely sepsis and inflammatory bowel disease, were highlighted to elucidate their roles in the acute and chronic inflammatory diseases. In cancer, exosomes orchestrate tumor microenvironment (TME) remodeling by facilitating angiogenesis, metastasis, and immune evasion through interactions with cancer-associated fibroblasts, tumor-associated macrophages, and extracellular matrix components. Furthermore, exosomes can facilitate the transition from inflammation to cancer by impacting pertinent signaling pathways via their transported oncogenic and inflammatory molecules. Tumor-derived exosomes also serve as non-invasive biomarkers correlating with disease progression. Clinically, exosomes demonstrate promise as therapeutic agents and drug carriers, evidenced by ongoing trials targeting inflammatory diseases and cancers. However, challenges in isolation standardization, scalable production, and understanding functional heterogeneity hinder clinical translation. Future research should prioritize elucidating cargo-specific mechanisms, optimizing engineering strategies, and advancing personalized exosome-based therapies. By bridging molecular insights with clinical applications, exosomes hold great potential in precision medicine for inflammation and oncology.

Keywords:  Cancer; Clinical translation; Exosomes; Inflammation; Microenvironment

DOI:  https://doi.org/10.1186/s43556-025-00280-9
Eur J Pharmacol. 2025 Jun 07. pii: S0014-2999(25)00577-1. [Epub ahead of print]1002 177823

Theranostics exosomes as autophagy mediators in cancer: Recent trends and advances.

Maryam Mojahedi, Mohammad Reza Tohidkia, Keyvan Kheyrolahzadeh, Ayuob Aghanejad.

  Autophagy plays dual roles in cancer, acting as both a tumor suppressor and a promoter. It maintains cellular integrity by removing damaged components to prevent tumor initiation; however, in established cancers, autophagy may facilitate tumor growth and survival under stress. This complexity highlights the potential of targeting autophagy to enhance the effectiveness of conventional treatments, such as chemotherapy and radiation. In this context, theranostic exosomes (EXOs) emerge as a pivotal advancement in precision medicine, functioning as both biomarkers and targeted drug delivery systems. Their unique ability to integrate therapeutic and diagnostic functions positions them at the forefront of personalized treatment strategies for cancer. Moreover, the interplay between EXOs and autophagy is vital for cellular communication and immune modulation, significantly influencing cancer progression and treatment outcomes. As research continues to explore EXO biology and its relationship with autophagy, challenges such as EXO extraction, cargo loading, and safety must be addressed to fully realize their clinical potential. Ultimately, a deeper understanding of the multifaceted roles of EXOs in mediating autophagy will pave the way for innovative therapeutic strategies aimed at restoring cellular homeostasis and improving patient outcomes.

Keywords:  Autophagy; Cancer; Exosome; Theranostics

DOI:  https://doi.org/10.1016/j.ejphar.2025.177823
J Orthop Surg Res. 2025 Jun 11. 20(1): 582

Research progress on exosomes from different sources in osteoarthritis and cartilage injury.

Zilong Yang, Zihao Deng, Wentao Gao, Wei Zhang, Xuxuan Fan, Ke Su, Zhiqin Liu.

  Exosomes are nanosized membrane vesicles secreted by cells that have garnered considerable attention in the biomedical field in recent years. Osteoarthritis (OA) is a common disabling joint disease with limited therapeutic options in clinical practice. Recent studies have shown that exosomes, as crucial mediators of intercellular communication, have proven effective in treating osteoarthritis and cartilage injury in vitro and in animal models. With ongoing research, exosomes have demonstrated tremendous potential in treating and even reversing osteoarthritis and cartilage injury. They may become an emerging therapeutic strategy in the future. This review primarily discusses the composition of exosomes and explores the potential mechanisms by which exosomes from different sources influence osteoarthritis and cartilage injury in the context of ongoing advances in exosome research. Furthermore, the review highlights the progress in exosome engineering for osteoarthritis Treatment to enhance the therapeutic efficacy of exosomes.

Keywords:  Cartilage; Cartilage injury; Cell-Free therapy; Exosomes; Extracellular vesicles; Osteoarthritis

DOI:  https://doi.org/10.1186/s13018-025-06000-x
Cell Signal. 2025 Jun 10. pii: S0898-6568(25)00351-1. [Epub ahead of print] 111936

ADSC exosomes improve high glucose induced fibroblast oxidative stress injury and accelerate DFU wound healing via regulating Keap1/Nrf2 axis.

Chenyang Tian, Huan Xu, Chunli Li, Jiaxue Gao, Hao Zhang, Peng Wang, Yuhang Wang, Dongyang Liu, Lan Jing, Bingang Wang, Wenjun Liu, Dongfa Liao, Junjie Li, Kuo Shen, Dahai Hu.

   BACKGROUND: Diabetic foot ulcer (DFU) is a common and challenging chronic disease that can lead to non-traumatic amputation. Studies have indicated that complex cellular environments in DFU often lead to the dysfunction of several cells at the wound site; however, the mechanism of this injury is still difficult to elucidate.
METHODS: DFU and normal skin tissue from patients were analyzed by pathological examination using hematoxylin and eosin (H&E), Masson, myeloperoxidase (MPO) and 8-Oxo-2'-deoxyguanosine (8OHdG) immunohistochemical staining. Extract and identify adipose-derived stem cell (ADSC) exosomes from ADSC culture medium. A diabetic wound healing model and a high-glucose-induced fibroblast cell model were used to analyze the effects of ADSC exosomes on DFU wound healing. In addition, collagen synthesis and fibrosis-related molecules as well as oxidative stress-related indices were detected in the cell model. To uncover the underlying mechanism, we further detected the expression of antioxidant related molecules, including Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4).
RESULTS: Pathological examination confirmed that DFU tissue displayed increased inflammatory cell infiltration and cell injury compared to normal skin. We confirmed that ADSC exosomes accelerated DFU wound healing and improved collagen synthesis and deposition. ADSC exosomes could reverse high glucose induced fibroblast damage, as well as the ability of collagen synthesis. Furthermore, our results indicated that ADSC exosomes improved HG-induced oxidative stress injury by regulating the expression of the Keap1/Nrf2 axis.
CONCLUSIONS: This study revealed that ADSC exosomes alleviated HG-induced fibroblast injury and accelerated diabetic wound healing by regulating the expression of the Keap1/Nrf2 axis.

Keywords:  ADSC exosomes; DFU; Fibroblast; Nrf2; ROS

DOI:  https://doi.org/10.1016/j.cellsig.2025.111936