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Extracellular vesicles (EVs) are cell-derived vesicles with a phospholipid bilayer measuring 50–150 nm in diameter with demonstrated therapeutic potentials. Limitations such as the natural biodistribution (mainly concentrated in the liver and spleen) and short plasma half-life of EVs present significant challenges to their clinical translation. In recent years, growing research indicated that engineered EVs with enhanced targeting to lesion sites have markedly promoted therapeutic efficacy. However, there is a dearth of systematic knowledge on the recent advances in engineering EVs for targeted delivery. Herein, we provide an overview of the targeting mechanisms, engineering techniques, and clinical translations of natural and engineered EVs in therapeutic applications. Enrichment of EVs at lesion sites may be achieved through the recognition of tissue markers, pathological changes, and the circumvention of mononuclear phagocyte system (MPS). Alternatively, external stimuli, including magnetic fields and ultrasound, may also be employed. EV engineering techniques that fulfill targeting functions includes genetic engineering, membrane fusion, chemical modification and physical modification. A comparative statistical analysis was conducted to elucidate the discrepancies between the diverse techniques on size, morphology, stability, targeting and therapeutic efficacy in vitro and in vivo. Additionally, a summary of the registered clinical trials utilizing EVs from 2010 to 2023 has been provided, with a full discussion on the perspectives. This review provides a comprehensive overview of the mechanisms and techniques associated with targeted delivery of EVs in therapeutic applications to advocate further explorations of engineered EVs and accelerate their clinical applications.
Extracellular vesicles (EVs) are cell-derived vesicles with a phospholipid bilayer measuring 50–150 nm in diameter with demonstrated therapeutic potentials. Limitations such as the natural biodistribution (mainly concentrated in the liver and spleen) and short plasma half-life of EVs present significant challenges to their clinical translation. In recent years, growing research indicated that engineered EVs with enhanced targeting to lesion sites have markedly promoted therapeutic efficacy. However, there is a dearth of systematic knowledge on the recent advances in engineering EVs for targeted delivery. Herein, we provide an overview of the targeting mechanisms, engineering techniques, and clinical translations of natural and engineered EVs in therapeutic applications. Enrichment of EVs at lesion sites may be achieved through the recognition of tissue markers, pathological changes, and the circumvention of mononuclear phagocyte system (MPS). Alternatively, external stimuli, including magnetic fields and ultrasound, may also be employed. EV engineering techniques that fulfill targeting functions includes genetic engineering, membrane fusion, chemical modification and physical modification. A comparative statistical analysis was conducted to elucidate the discrepancies between the diverse techniques on size, morphology, stability, targeting and therapeutic efficacy in vitro and in vivo. Additionally, a summary of the registered clinical trials utilizing EVs from 2010 to 2023 has been provided, with a full discussion on the perspectives. This review provides a comprehensive overview of the mechanisms and techniques associated with targeted delivery of EVs in therapeutic applications to advocate further explorations of engineered EVs and accelerate their clinical applications.
Background: Recent interest in plant-derived exosome-like nanoparticles (ENs) has surged due to their therapeutic potential, which includes antioxidant, anti-inflammatory, and anticancer activities. These properties are attributed to their cargo of bioactive metabolites and other endogenous molecules. However, the properties of ENs isolated from plant cell cultures remain less explored. Methods: In this investigation, grape callus-derived ENs (GCENs) were isolated using differential ultracentrifugation techniques. Structural analysis through electron microscopy, nanoparticle tracking analysis, and western blotting confirmed that GCENs qualify as exosome-like nanovesicles. Results: These GCENs contained significant amounts of microRNAs and proteins characteristic of plant-derived ENs, as well as trans-δ-viniferin, a notable stilbenoid known for its health-promoting properties. Functional assays revealed that the GCENs reduced the viability of the triple-negative breast cancer cell line MDA-MB-231 in a dose-dependent manner. Moreover, the GCENs exhibited negligible effects on the viability of normal human embryonic kidney (HEK) 293 cells, indicating selective cytotoxicity. Notably, treatment with these GCENs led to cell cycle arrest in the G1 phase and triggered apoptosis in the MDA-MB-231 cell line. Conclusions: Overall, this study underscores the potential of grape callus-derived nanovectors as natural carriers of stilbenoids and proposes their application as a novel and effective approach in the management of cancer.
Neurodegenerative diseases are characterized by brain lesions that limit normal daily activities and represent a major challenge to healthcare systems worldwide, with a significant economic impact. Nanotechnology is the science of manipulating matter at the nanoscale, where materials exhibit unique properties that are significantly different from their larger counterparts. These properties can be exploited for a wide range of applications, including medicine. Among the emerging therapeutic approaches for the treatment of neurodegenerative diseases, nanotechnologies are gaining prominence as a promising avenue to explore. Here, we review the state of the art of biological and artificial vesicles and their biological properties in the context of neurodegenerative diseases. Indeed, nanometric structures such as extracellular vesicles and artificial vesicles represent a promising tool for the treatment of such disorders due to their size, biocompatibility, and ability to transport drugs, proteins, and genetic material across the blood–brain barrier to target specific cells and brain areas. In the future, a deeper and broader synergy between materials science, bioengineering, biology, medicine, and the discovery of new, increasingly powerful delivery systems will certainly enable a more applied use of nanotechnology in the treatment of brain disorders.
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