bims-engexo 2025-02-23 papers

Med Oncol. 2025 Feb 17. 42(3): 77

Exosomes and solid cancer therapy: where are we now?

Tomas Zemanek, Lubos Danisovic, Andreas Nicodemou.

Cancer immunotherapy has revolutionized oncology, offering new hope for patients with previously incurable cancers. However, solid tumors remain a significant challenge due to immune evasion, therapeutic resistance, and the immunosuppressive tumor microenvironment. Exosomes, a specialized subset of extracellular vesicles, have emerged as promising tools in cancer therapy owing to their unique role in intercellular communication and immune modulation. These vesicles transport antigens, major histocompatibility complex (MHC) molecules, and immune-modulatory cargo, positioning them as potential platforms for cancer vaccines, drug delivery systems, and combinatorial therapies. Advances in engineered exosomes have improved drug bioavailability, tumor targeting, and immune stimulation, showcasing their potential in personalized medicine. This review highlights their multifaceted role in the tumor microenvironment, and their mechanisms of action in solid cancer therapy. Additionally, we discuss emerging strategies to overcome clinical and technical hurdles, paving the way for novel and effective cancer treatments.

Keywords: Cancer; Cell therapy; Drug delivery system; Exosomes; Immunotherapy; Personalized medicine

DOI: https://doi.org/10.1007/s12032-025-02626-3

MedComm (2020). 2025 Mar;6(3): e70095

Exosomes: a double-edged sword in cancer immunotherapy.

Jiayi Chen, Siyuan Hu, Jiayi Liu, Hao Jiang, Simiao Wang, Zhaogang Yang.

Over the past few decades, immunotherapy has emerged as a powerful strategy to overcome the limitations of conventional cancer treatments. The use of extracellular vesicles, particularly exosomes, which carry cargoes capable of modulating the immune response, has been extensively explored as a potential therapeutic approach in cancer immunotherapy. Exosomes can deliver their cargo to target cells, thereby influencing their phenotype and immunomodulatory functions. They exhibit either immunosuppressive or immune-activating characteristics, depending on their internal contents. These exosomes originate from diverse cell sources, and their internal contents can vary, suggesting that there may be a delicate balance between immune suppression and stimulation when utilizing them for immunotherapy. Therefore, a thorough understanding of the molecular mechanisms underlying the role of exosomes in cancer progression is essential. This review focuses on the molecular mechanisms driving exosome function and their impact on the tumor microenvironment (TME), highlighting the intricate balance between immune suppression and activation that must be navigated in exosome-based therapies. Additionally, it underscores the challenges and ongoing efforts to optimize exosome-based immunotherapies, thereby making a significant contribution to the advancement of cancer immunotherapy research.

Keywords: exosome; immune stimulatory; immune suppressive; tumor

DOI: https://doi.org/10.1002/mco2.70095

Mater Today Bio. 2025 Apr;31 101528

Physically engineered extracellular vesicles targeted delivering miR-21-5p to promote renoprotection after renal ischemia-reperfusion injury.

Di Wu, Wenjie Ma, Liucheng Wang, Chengcheng Long, Silin Chen, Jingyu Liu, Yiguan Qian, Jun Zhao, Changcheng Zhou, Ruipeng Jia.

Acute kidney injury (AKI) resulting from ischemia-reperfusion injury (IRI) is a common challenge in various clinical practices, yet effective therapies remain elusive. Endothelial injury plays a crucial role in the pathogenesis of renal IRI. Endothelial progenitor cells (EPCs) derived extracellular vesicles (EVs) hold promise as cell-free therapies for treating renal IRI; however, their efficacy is limited by low delivery efficiency. In this study, we developed neutrophils (NEs) membrane-modified EVs (N-EVs) by exploiting the natural properties of NEs to target damaged endothelium. N-EVs inherited the characteristic membrane proteins of NEs along with the biological functions of EPCs-EVs. Results from in vitro and in vivo experiments demonstrated that N-EVs significantly enhanced the targeting efficiency of EVs towards IRI kidneys via P-selectin glycoprotein ligand-1 (PSGL-1). Moreover, N-EVs effectively promoted the proliferation, migration, and tube-formation abilities of injured endothelial cells (ECs) and contributed to overall renal function improvement in IRI kidneys through targeted delivery of miR-21-5p. Additionally, N-EVs could restore damaged endothelial integrity, reduce cytokine release, and inhibit leukocyte infiltration, hence alleviating renal inflammation. In conclusion, our accessible engineering approach represents a promising strategy for treating renal IRI. Furthermore, this membrane hybrid modification can be tailored and optimized for broader applications in treating other diseases.

Keywords: Cell membrane; Engineering; Extracellular vesicle; Neutrophil; Renoprotection; miRNAs

DOI: https://doi.org/10.1016/j.mtbio.2025.101528

Chem Bio Eng. 2025 Jan 23. 2(1): 3-22

Engineered Extracellular Vesicles as a New Class of Nanomedicine.

Xiaowei Wen, Zerun Hao, Haofan Yin, Jie Min, Xueying Wang, Sihan Sun, Gang Ruan.

Extracellular vesicles (EVs) are secreted from biological cells and contain many molecules with diagnostic values or therapeutic functions. There has been great interest in academic and industrial communities to utilize EVs as tools for diagnosis or therapeutics. In addition, EVs can also serve as delivery vehicles for therapeutic molecules. An indicator of the enormous interest in EVs is the large number of review articles published on EVs, with the focus ranging from their biology to their applications. An emerging trend in EV research is to produce and utilize "engineered EVs", which are essentially the enhanced version of EVs. EV engineering can be conducted by cell culture condition control, genetic engineering, or chemical engineering. Given their nanometer-scale sizes and therapeutic potentials, engineered EVs are an emerging class of nanomedicines. So far, an overwhelming majority of the research on engineered EVs is preclinical studies; there are only a very small number of reported clinical trials. This Review focuses on engineered EVs, with a more specific focus being their applications in therapeutics. The various approaches to producing engineered EVs and their applications in various diseases are reviewed. Furthermore, in vivo imaging of EVs, the mechanistic understandings, and the clinical translation aspects are discussed. The discussion is primarily on preclinical studies while briefly mentioning the clinical trials. With continued interdisciplinary research efforts from biologists, pharmacists, physicians, bioengineers, and chemical engineers, engineered EVs could become a powerful solution for many major diseases such as neurological, immunological, and cardiovascular diseases.

DOI: https://doi.org/10.1021/cbe.4c00122

Chem Commun (Camb). 2025 Feb 19.

Engineered extracellular vesicles: an emerging nanomedicine therapeutic platform.

Jingshi Tang, Dezhong Li, Rui Wang, Shiwei Li, Yanlong Xing, Fabiao Yu.

The intercellular communication role of extracellular vesicles has been widely proved in various organisms. Compelling evidence has illustrated the involvement of these vesicles in both physiological and pathological processes. Various studies indicate that extracellular vesicles surpass conventional synthetic drug carriers, owing to their abundance in organisms, enhanced targeting ability and low immunogenicity. Therefore, extracellular vesicles have been deemed to be potential drug carriers for the treatment of various diseases, and related studies have increased rapidly. Here, we intend to provide a comprehensive and in-depth review of recent advances in the sources, delivery function, extraction and cargo-loading technologies of extracellular vesicles, as well as their clinical potential in constructing emerging nanomedicine therapeutic platforms. In particular, microfluidic-based isolation and drug-loading technologies, as well as the treatment of various diseases, are highlighted. We also make comparisons between extracellular vesicles and other conventional drug carriers and discuss the challenges in developing drug delivery platforms for clinical translation.

DOI: https://doi.org/10.1039/d4cc06501h