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Abstract

Background: Exosomes are membrane-enclosed nanosized vesicles of endosomal origin, ranging from 30 to 150 nanometers in diameter, that are constitutively secreted by virtually all cell types and serve as intercellular communication vehicles through the transfer of proteins, lipids, messenger RNA, microRNA, and non-coding RNA between donor and recipient cells. Their natural origin, intrinsic biocompatibility, capacity to traverse biological barriers including the blood-brain barrier, low immunogenicity, and ability to carry diverse molecular cargo make exosomes highly attractive as drug delivery vehicles. Unlike synthetic nanoparticles, exosomes carry a biological membrane studded with surface proteins that mediate cell-type-specific recognition, uptake, and biological activity in recipient cells, providing a degree of inherent tissue targeting that must be engineered into synthetic systems from scratch.


Objective: This review critically examines the biogenesis, composition, isolation methods, drug loading strategies, surface engineering approaches, characterization techniques, mechanisms of cellular uptake and cargo delivery, and therapeutic applications of exosomes in cancer therapy, inflammatory disease, and neurological conditions, with emphasis on research published up to 2022.


Results and Discussion: Exosomes derived from mesenchymal stem cells, dendritic cells, macrophages, tumor cells, and plant sources have been investigated as natural drug delivery vehicles. Drug loading by electroporation, sonication, co-incubation, and membrane fusion enables encapsulation of small molecules, nucleic acids, and proteins. Surface engineering with targeting ligands, cell-penetrating peptides, and antibody fragments enhances organ and cell-type specificity. Exosome-based delivery of doxorubicin, siRNA, miRNA, and therapeutic proteins has demonstrated superior tumor accumulation, blood-brain barrier penetration, and therapeutic efficacy compared to equivalent free drug or synthetic nanoparticle formulations in preclinical cancer and CNS disease models.


Conclusion: Exosomes represent a biologically sophisticated drug delivery platform whose natural origin confers inherent advantages in biocompatibility, immune evasion, and barrier penetration that are difficult to replicate with synthetic systems. Significant manufacturing, standardization, and regulatory challenges must be addressed before exosome-based drug delivery products can realize their considerable clinical potential.

Keywords

Exosomes; extracellular vesicles; drug delivery; cancer therapy; siRNA delivery; blood-brain barrier; biomimetic nanocarriers; mesenchymal stem cell exosomes; exosome engineering; tumor targeting

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