Exosomes-mediated intercellular communication and their theragnostic potential against cancer and related disorders:...

Exosomes, a specialized group of extracellular vesicles (EVs) ranging from 30 to 150 nm in size, have emerged as important mediators of intercellular communication across both mammalian and plant kingdoms. By facilitating the transfer of bioactive cargo, these vesicles orchestrate complex signalling networks essential for physiological homeostasis and pathological progression. Extensive research into both plant and mammalian exosomes has established their inherent biocompatibility and potential as cell-free systems for the targeted delivery of therapeutic drugs in the management of various diseases, including cancer. Moreover, exosomes have unique molecular signatures that enable the identification of their cell of origin and serve as high-fidelity biomarkers for precise disease diagnosis. This review provides a comprehensive overview of exosomal biology, beginning with the critical importance of standardized isolation and enrichment protocols to ensure sample purity and yield. This review also evaluates contemporary detection and characterization methodologies, ranging from nanoparticle tracking analysis to super-resolution microscopy, which are essential for defining exosomal identity. Moreover, the dual role of exosomes in cancer and disease progression, emphasizing their ability to modulate the tumour microenvironment and serve as non-invasive biomarkers for liquid biopsies, has also been explored. Bioengineering strategies such as genetic manipulation of the host cell or chemical modification of the exosome surface, can enhance their targeting precision and therapeutic loading capacity. The review also discusses the capacity of these vesicles to be loaded with exogenous drugs, including small molecules and RNA-based therapeutics, transforming them into potent, site-specific delivery vehicles. Despite their immense potential as biocompatible, cell-free drug delivery vehicles, several translational hurdles, including large-scale manufacturing consistency and regulatory complexities, remain as significant challenges, which if addressed, can lead to a shift toward personalized exosome-based diagnosis and therapy that could revolutionize the management of cancer and other complex systemic disorders.