Extracellular vesicles (EVs) mediate cell-to-cell communication via the transfer of biomolecules locally and systemically between organs. It has been elucidated that the specific EV cargo load is fundamental for cellular response upon EV delivery. Therefore, revealing the specific molecular machinery that functionally regulates the precise EV cargo intracellularly is of importance in understanding the role of EVs in physiology and pathophysiology and conveying therapeutic use. The purpose of this review is to summarize recent findings on the general rules, as well as specific modulator motifs governing EV cargo loading. Finally, we address available information on potential therapeutic strategies to alter cargo loading.

Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo.

Recent progresses in exosome-based systems for targeted drug delivery to the brain.

Extracellular vesicles (EVs) are a heterogeneous group of membrane-enclosed structures produced by prokaryotic and eukaryotic cells. EVs carry a range of biological cargoes, including RNA, protein, and lipids, which may have both metabolic significance and signalling potential. EV release has been suggested to play a critical role in maintaining intracellular homeostasis by eliminating unnecessary biological material from EV producing cells, and as a delivery system to enable cellular communication between both neighbouring and distant cells without physical contact. In this review, we give an overview of what is known about the relative enrichment of the different types of RNA that have been associated with EVs in the most recent research efforts. We then examine the selective and non-selective incorporation of these different RNA biotypes into EVs, the molecular systems of RNA sorting into EVs that have been elucidated so far, and the role of this process in EV-producing cells. Finally, we also discuss the model systems providing evidence for EV-mediated delivery of RNA to recipient cells, and the implications of this evidence for the relevance of this RNA delivery process in both physiological and pathological scenarios. 

/pdf/unpacking-extracellular-vesicles-rna-cargo-loading-and-1jczdqfa.pdf

Unpacking extracellular vesicles: RNA cargo loading and function

Extracellular vesicles (EVs) have recently emerged as crucial modulators of cancer drug resistance. Indeed, it has been shown that they can directly sequester anti-tumor drugs, decreasing their effective concentration at target sites. Moreover, they facilitate the horizontal transfer of specific bioactive cargoes able to regulate proliferative, apoptotic, and stemness programs in recipient cells, potentially conferring a resistant phenotype to drug-sensitive cancer cells. Finally, EVs can mediate the communication between the tumor and both stromal and immune cells within the microenvironment, promoting treatment escape. In this context, clarifying the EV-driven resistance mechanisms might improve not only tumor diagnosis and prognosis but also therapeutic outcomes. Detailed cellular and molecular events occurring during the development of EV-mediated cancer drug resistance are described in this review article.

https://www.mdpi.com/2072-6694/13/4/749/pdf

Extracellular Vesicles: Emerging Modulators of Cancer Drug Resistance.

Extracellular vesicles (EVs) are naturally phospholipid enclosed nanovesicles released by many cells in the body. They are stable in circulation, have low immunogenicity, and act as carriers for functionally active biological molecules. They interact with target organs and bind to the receptors. Their target specificity is important to use EVs as noninvasive diagnostic and prognostic tools. EVs play a vital role in normal physiology and cellular communication. They are known to protect their cargo from degradation, which makes them important drug carriers for targeted drug delivery. Using EVs with markers and tracking their path in systemic circulation can be revolutionary in using them as diagnostic tools. We will discuss the scope of this in this paper. Although there are limitations in EVs isolation and storage, their high biocompatibility will fuel more innovations to overcome these challenges.

https://journals.sagepub.com/doi/pdf/10.1177/15330338211041203

Diagnostic and Therapeutic Potential of Extracellular Vesicles.

The Challenges and Possibilities of Extracellular Vesicles as Therapeutic Vehicles

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The Challenges and Possibilities of Extracellular Vesicles as Therapeutic Vehicles