# Extracellular Vesicles and Artificial Intelligence: Unique Weapons against Breast Cancer
## 2 EVs in Breast Cancer
### Exosomes as a Weapon in Precision Medicine  
The field of EVs is highly speculative because the characterization of EVs' contents, such as proteins and miRNAs, and their expression levels can be used as candidate markers for early detection, relapse, and metastasis prediction, such as susceptibility to therapeutic treatment in BC patients. Highly stratified by type and status, with a highly heterogeneous nature, BC is treated with typical approaches such as surgery and chemo/radio/hormone therapy but not personalized medicine [114; 115; 116; 117; 118; 119; 120; 121; 122; 123; 124; 125; 126]. The enrichment of protocols useful for obtaining and characterizing EVs through the arrival of cutting-edge technologies and the ease of isolating EVs from many biological matrices (blood, urine, milk, lymphatic exudate, etc.) in a noninvasive manner make them good candidates for biomarkers alone or in association with other emerging markers for different cancers [127; 128; 129; 130; 131; 132; 133]. The information obtained via the EVs' fluid characterization can be useful and applied in BC diagnosis, monitoring after surgical resection, and during neoadjuvant/adjuvant therapy. The research led to the identification of several cancer-related markers (CD24, CD29, CD44, and CD146) and platelet markers (CD41b, CD42a, and CD62p) on EVs of potential interest as biomarkers; however, further characterizations are needed [66]. Many studies promote some markers EVs, in particular circulating EVs, as tools for several tumor diagnoses and prognostic biomarkers [120; 121; 122; 123; 124; 125; 126; 127; 128; 129; 130; 131; 132; 133]. EVs' low immune response and tolerability in the body, ease of internalization with the release of carried macromolecules, and ability to cross the blood-brain barrier due to their small size make them a good vehicle for drug delivery in precision medicine [136; 137]. Although there are excellent prospects for the use of EVs, there still appear to be limitations, in part due to the half-life of the nanoparticles. In 2019, [PERSON] et al. highlighted that the length of time for the clearance of exosomes from the blood of wild-type and CD169\({}^{-/-}\) mice was \(\sim\)2 min, but a longer-lived reservoir of exosomes was present after 120 min in the spleen, although the majority of exosomes had been cleared from circulation [138]. The topical application of exosomes (buccal mucosa or ocular surface) shows a shorter exosome half-life caused by the rapid fluid turnover (saliva or tears) and the exposition of external elements. Due to the rapid clearance rate of circulating exogenous exosomes and consequently poor exosome enrichment in the target tissue, several studies in the literature promote strategies to increase the exosomes' half-life in circulation. However, in vivo exosome half-life and clearance are closely associated with administrative methods, the availability of recipient cells for EV internalization, the size of the EVs, and the cell-type origin [139]. It is known that the exposition of CD47 proteins upon an exosome's surface represents \"don't eat me\" signaling, evading the monocytes' phagocytosis with an increase in circulating exosomes [140]. The latest evidence suggests a hydrogel, an absorbable biological scaffold, as a vehicle able to achieve the stability and biological activity of exosomes [141]. In particular, hyaluronic-acid-based hydrogels have been used for a long time as an exosome delivery strategy in bone regeneration applications [142]. In particular, in Table 1, the main miRNAs and EV-derived biomarkers implicated in the diagnosis, prognosis, and drug sensitivity of BC and variations in their relative expression levels are shown.