Exosomes: from basic research to clinical diagnostic and therapeutic applications in cancer

Abstract

Cancer continues to pose a global threat despite potent anticancer drugs, often accompanied by undesired side effects. To enhance patient outcomes, sophisticated multifunctional approaches are imperative. Small extracellular vesicles (EVs), a diverse family of naturally occurring vesicles derived from cells, offer advantages over synthetic carriers. Among the EVs, the exosomes are facilitating intercellular communication with minimal toxicity, high biocompatibility, and low immunogenicity. Their tissue-specific targeting ability, mediated by surface molecules, enables precise transport of biomolecules to cancer cells. Here, we explore the potential of exosomes as innovative therapeutic agents, including cancer vaccines, and their clinical relevance as biomarkers for clinical diagnosis. We highlight the cargo possibilities, including nucleic acids and drugs, which make them a good delivery system for targeted cancer treatment and contrast agents for disease monitoring. Other general aspects, sources, and the methodology associated with therapeutic cancer applications are also reviewed. Additionally, the challenges associated with translating exosome-based therapies into clinical practice are discussed, together with the future prospects for this innovative approach.

Keywords: Biomarkers; Cancer; Clinical trials; Drug delivery; Exosomes; Treatment.

Fig. 1

Hallmarks of cancer, timeline and exosome biogenesis. A The hallmarks of cancer. Adapted from Hanahan and Weinberg [3]. B Exosome biogenesis with a size ranging from 30 to 150 nm. Adapted from Colombo et al. [14]. C Timeline of the more representative events in the EV field. Adapted from Couch et al. [12]

Fig. 2

Overview of engineered exosome constructs and their role in modulating antitumor immune responses. Different cells are the sources (blue box) for engineer exosomes involved in immunosuppression or targeting immune checkpoints while others act as a cancer vaccine (green box). The immune response generated by each type of exosome is indicated by arrows in a variety of colors (brown box). TDEs acts cause immunosuppression while activation of DCs by the engineer exosomes initiates a cascade that stimulates T lymphocytes, amplifying the antitumor immune response. Acting on immune checkpoints throughout exosomes led to M2 to M1 macrophage transition

Fig. 3

Schematic illustration of small EVs large production steps. The process begins with the production of different types of EVs with a special focus on exosomes, including native, hybrid, and synthetic EVs. These EVs are then subjected to scalable isolation methods to ensure reproducibility. Following isolation, storage protocols are implemented to address batch-to-batch variations, ensuring consistency in the final product. EVs undergo purification to remove contaminants and improve quality. Critical steps also include drug loading and functionalization of exosomes to enhance their therapeutic potential. Before clinical application, these EVs are tested in preclinical studies to assess their efficacy and safety. Finally, rigorous quality control measures are conducted to ensure that the exosomes meet the required standards for clinical use in humans. The color-coded bar indicates the current state of the information and technology known in every production step. Purple color (high) means technological development and detailed examples in the literature, yellow (medium) highlights the need for additional studies, and light blue (low) implies the need for additional basic and comparative research