Exosomes and Extracellular Vesicles in Oncology: Next-Generation Smart Nanocarriers for Precision Cancer Therapy.

Exosomes are an evolved sub-type of extracellular vesicles (EVs) that have gained popularity in recent years as a novel biological nanocarrier system for targeted precision therapy in cancer owing to their excellent biocompatibility, low immunogenicity, and high stability. While other artificial systems can only deliver specific types of drug, exosomes have been found to effectively carry different types of therapeutic cargo, such as chemotherapeutic agents, proteins, peptides, mRNA, siRNA, miRNA, and even CRISPR/Cas gene editing elements. Recent progress in exosome engineering technologies, such as surface modification, donor cell modification, bionic hybrid vesicles, and stimuli-responsive exosomes, has improved their targeting efficacy, cargo-loading capacity, and controlled drug release properties. Apart from their therapeutic use, exosomes play an active role in promoting tumor development by regulating the tumor microenvironment, angiogenesis, metastasis, immune escape, maintenance of cancer stem cells, and drug resistance. This review provides a brief insight into the biological properties of exosomes, recent developments in isolation and characterization methods, engineering approaches, therapeutic cargo loading, and their uses in targeted chemotherapy, gene and RNA therapy, immunotherapy, phototherapy, sonodynamic therapy, chemo-dynamic therapy, and combinational therapy. Moreover, the existing issues in exosome research, such as exosome heterogeneity, large-scale production, quality control, and regulatory issues, are addressed. Finally, new approaches involving artificial intelligence, multi-omics technology, and personalized engineering of exosomes are presented as potential solutions to enhance the clinical use of exosomes.