In 1983, two separate research groups reported novel observations regarding small, extracellular vesicles released by maturing red blood cells.1,2 Five years later, the vesicles were named exosomes by Rose Johnstone, an author from one of the original studies.3 On reflection, Johnstone describes her groups early discovery as somewhat accidental, explaining they stumbled upon exosomes when they were looking for an appropriate system to identify a specific transport protein.4 According to Johnstone, reports of the observation were initially met with disbelieving eyes.Now, the initial skepticism has been overcome; instead of being considered an artifact, exosome formation is now accepted as a natural phenomenon. As biologists race to unlock the potential of exosomes, research in the field continues to gain momentum; enter exosomes in the PubMed search box and you will see over 4000 results from 2020 alone (up from 265 results in 2010). In this article, we provide an overview of the biology of exosomes and explore their potential uses as diagnostic and therapeutic tools a market now valued at over $41 million and projected to reach $358.91 million by 2027.

Live reporters like these can reveal unexpected cellular behaviors by allowing real-time visualization of the secretion and interaction of exosomes with cells. Although we know exosomes are important for directional migration, we were surprised by how closely the cells followed the exosome trails as if the exosomes were releasing an attracting factor or pheromone.

For Wafa Al-Jamal, reader in nanomedicine and drug delivery at Queens University Belfast School of Pharmacy, Northern Ireland, UK, exosome mimetics represent a way forward in her mission to develop personalized, effective and safe nanomedicines targeting metastatic prostate cancer. Our vision, says Al-Jamal, is to engineer targeted exosome mimetics from patients' blood cells, so the treatment is customized for each patient. Al-Jamal notes how challenging it has been to deliver effective doses of chemotherapeutics to metastatic lesions especially in bone without causing toxicity to healthy tissues. The approach, described recently in the Journal of Controlled Release, aims to improve drug delivery by targeting drug-loaded exosome mimetics to advanced and metastatic prostate cancer lesions by combining the intrinsic affinity of exosome mimetics with active targeting via prostate-specific membrane antigen (PSMA).29Our approach is based on filtering whole monocyte cells into smaller cell-mimetic vesicles using different pore size membranes, which generates vesicles similar to naturally-secreted extracellular vesicles (e.g., exosomes) but accelerates production and increases yield, explains Al-Jamal. Moreover, our approach aims to prepare targeted vesicles expressing a prostate-targeting ligand on the cells' surface, eliminating the chemical procedures that would otherwise be required to attach the targeting ligand to the vesicles surface.

Exosome mimetics also provide an opportunity for theranostics, i.e., the combination of diagnostic and therapeutic applications to predict therapy outcomes in animal models and patients. Al-Jamal explains how the co-delivery of diagnostics and therapeutics in a single nanocarrier could be achieved: Due to the vesicular nature of exosome mimetics, drugs and imaging agents could be co-loaded into the same vesicles. Alternatively, imaging agents could be conjugated to the vesicles surface.

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Why Exosomes Are Being Explored as Diagnostic and Therapeutic Tools - Technology Networks