bims-exocan 2026-03-22 papers

Issue of 2026–03–22
five papers selected by
Muhammad Rizwan, COMSATS University

Biochem Biophys Res Commun. 2026 Feb 26. pii: S0006-291X(26)00297-4. [Epub ahead of print]812 153533

Emerging strategies in exosome engineering: From cellular preconditioning to hybridization for targeted therapeutics.

Exosomes are nanosized extracellular vesicles that originate from all cell types. They have a precious role in intercellular communication and therapeutic delivery. Exosomes are considered attractive candidates because of their innate biocompatibility, low immunogenicity, and ability to transport bioactive molecules across biological barriers. However, some challenges are related to the clinical application of native exosomes. These challenges have led to advances in the engineering of exosomes. Surface modifications, cargo loading techniques, and hybridization with synthetic materials are some examples of these modifications. This review article explores innovative strategies to enhance the therapeutic potential of these exosomes. It focuses on modifying stem cells during the culture phase using techniques such as hypoxic preconditioning, chemical stimulation, and biophysical stimulation, which have been shown to optimize the quantity and biological activity of exosomes. Additionally, post-production modifications, including surface functionalization, hybridization with synthetic materials, and cargo enhancement, are being investigated for their role in improving the stability, targeting specificity, and therapeutic efficacy of exosomes. Together, these insights offer a roadmap for realizing the full potential of exosomes as next-generation delivery tools in nanomedicine.

Keywords: Cell engineering; Drug delivery systems; Exosomes; Molecular targeted therapy; Nanomedicine

DOI: https://doi.org/10.1016/j.bbrc.2026.153533

Apoptosis. 2026 Mar 19. pii: 106. [Epub ahead of print]31(3):

The circTIMP2/miR-106a/TIMP2 tumor-suppressive axis versus tumor-derived exosomal counteraction in gastric cancer.

Meng Zhu, Xinwei Dong, Ning Zhang, Ningbo Huang, Zenghui Zhu, Jingwei Ma.

Gastric cancer is a multifactorial disease and remains one of the leading causes of cancer-related deaths worldwide. CircRNAs have emerged as critical regulators in various cancers, while exosomes play essential roles in shaping the tumor microenvironment. However, the function of circTIMP2 and its interaction with exosomes are largely unknown. In this study, we evaluated the expression of circTIMP2 and investigated its biological roles in gastric cancer through a series of in vitro and in vivo experiments. The sponge mechanism of circTIMP2 for miR-106a, together with the target TIMP2, was validated using bioinformatics, luciferase, RNA immunoprecipitation, and fluorescence in situ hybridization assays. The involvement of exosomes and the influence on circTIMP2 were further explored. We found that circTIMP2 was significantly downregulated in gastric cancer, whereas miR-106a was upregulated, accompanied by downregulation of TIMP2. Overexpression of circTIMP2 attenuated malignant behaviors of cancer cells and suppressed subcutaneous tumor growth by upregulating its host gene TIMP2, coinciding with reduced miR-106a and inhibition of Wnt/β-catenin signaling pathway. Mechanistically, circTIMP2 acts as a competitive endogenous RNA by sequestering miR-106a to release its target TIMP2, thereby forming a circTIMP2/miR-106a/TIMP2 feedback loop that suppresses gastric cancer through inhibition of Wnt/β-catenin signaling. Importantly, tumor-derived exosomes counteracted the suppressive effects of circTIMP2, promoting orthotopic tumor progression by inhibiting TIMP2 and reactivating Wnt/β-catenin signaling. Our findings unveil a novel circRNA-guided feedback loop in gastric cancer and highlight how exosome-mediated mechanisms counteract this axis, providing new insights into the molecular pathogenesis of gastric cancer and suggesting potential therapeutic targets.

Keywords: Exosomes; Gastric cancer; ceRNA; circRNA; miRNA

DOI: https://doi.org/10.1007/s10495-026-02297-z

Int J Nanomedicine. 2026 ;21 582197

Exosomes as Cellular Communicators and Therapeutic Agents in Orthopedic Diseases: From Mechanisms to Intervention.

Jianwen Zhang, Minjie Zhang, Xiaoru Ren, Mengying Li, Yiwen Zhu, Dan Shou, Yang Zhang.

Exosome-mediated intercellular communication has become a critical mechanism in the pathogenesis, progression, and regenerative repair of orthopedic diseases. By delivering bioactive molecules, exosomes dynamically regulate bone remodeling, cartilage homeostasis, and inflammatory responses-processes that are commonly disrupted in conditions such as osteoporosis, osteoarthritis, and bone non-union. Current therapeutic approaches often fail to achieve complete tissue repair or reverse disease progression, representing a major clinical challenge in orthopedics. This systematic review examines how exosome secretion, cargo loading, and cellular uptake are modulated by physical, chemical, biological, and pharmacological factors, thereby influencing disease progression and tissue repair. Furthermore, we evaluate the translational potential of engineered exosomes as targeted therapeutic strategies and analyze the dual dilemmas currently faced in exosome research and clinical translation: on one hand, exosomes themselves encounter technical bottlenecks such as standardization of isolation, drug-loading efficiency, large-scale production, and targeted delivery; on the other hand, their clinical application remains limited by unclear in vivo metabolic mechanisms, lack of efficacy evaluation systems, and insufficient clinical validation. Overcoming these challenges will be essential to advancing the real-world clinical application of exosomes in orthopedics.

Keywords: exosomes; intercellular communication; orthopedic diseases

DOI: https://doi.org/10.2147/IJN.S582197

Int J Nanomedicine. 2026 ;21 570252

Extracellular Vesicles as Emerging Drug Delivery Platforms in Triple-Negative Breast Cancer: A Systematic Review.

Jiao Tian, Yun Zhi Chin, Min Hwei Ng, Kok Lun Pang, Jia Xian Law.

Breast cancer is the most prevalent malignancy among women, with triple-negative breast cancer (TNBC) being the most aggressive subtype. The lack of standard targeted therapies necessitates reliance on chemotherapy, which often suffers from poor targeting and significant off-target toxicity. This systematic review evaluates the therapeutic potential of drug delivery systems based on extracellular vesicles (EVs) for TNBC using 17 studies from 2020 to 2024 published in Scopus, PubMed, and Web of Science. The review discusses the diverse therapeutic cargos delivered by EVs, including chemotherapeutic agents and nucleic acids, while emphasizing the need for standardized protocols to facilitate EV isolation and characterization. Key findings provide both in vitro and in vivo evidence of the efficacy of EV-based therapies against TNBC cell lines and animal models, alongside insights into engineering strategies that enhance targeting specificity. Despite the promising findings, challenges remain in clinical translation, such as technical limitations and inconsistent reporting. The results underscore the potential of EVs to revolutionize TNBC treatment strategies, paving the way for more effective therapeutic options.

Keywords: breast cancer; chemotherapy; drug delivery system; exosome; precision medicine

DOI: https://doi.org/10.2147/IJN.S570252

J Nanobiotechnology. 2026 Mar 17.

Engineering BiTE-inspired IPSC-exosomes to potentiate CAR-T cell therapy against lung cancer.

Ronghao Wang, Guining Fu, Haozhao Dou, Mingyuan Hu, Zhanglin Li, Junwen Gan, Jiasheng He, Xiaojian Li, Guihong Zhang, Xianjun Li, Tianchuan Zhu, Qingdong Cao.

Chimeric antigen receptor T (CAR-T) cell therapy faces critical barriers in solid tumors, including poor infiltration, T cell exhaustion, and immunosuppressive microenvironments, resulting in response rates below 10%. Herein, we engineered an inhalable nanoplatform using induced pluripotent stem cell-derived exosomes (IEXOs) displaying bispecific PD-1/mesothelin (MSLN) single-chain variable fragments (scFv) and loaded with indole-3-propionic acid (IPA) for metabolic reprogramming. IEXOs demonstrated high yield and intrinsic antitumor properties, inhibiting Lewis lung carcinoma (LLC) cell proliferation and migration. The bispecific exosomes loaded with IPA (BIEXO@IPA) achieved efficient pulmonary delivery via nebulization with 79.3% tumor cell-specific uptake versus 47.9% for liposomes in orthotopic lung cancer models. BIEXO@IPA treatment reduced tumor burden by 87.9% and achieved 80% survival at 80 days. Mechanistically, BIEXO@IPA bridged PD-1+ T cells to MSLN+ tumor cells through bispecific engagement while expanding progenitor exhausted T (Tpex) cells and reducing regulatory T cells. When combined with CAR-T cells, BIEXO@IPA achieved 66.7% complete remission with 100% survival at 80 days and 83.3% resistance to tumor rechallenge. Safety assessments revealed minimal toxicity. This BIEXO@IPA platform represents a scalable, clinically translatable strategy that addresses fundamental CAR-T limitations in solid tumors through synergistic multimodal immunomodulation.

Keywords: Bispecific T cell engagers; Chimeric antigen receptor T cells; Exosomes; Immunotherapy; Indole-3-propionic acid; Induced pluripotent stem cells; Lung cancer

DOI: https://doi.org/10.1186/s12951-026-04242-3