**5. Conclusions**

Altogether, EVs are prospective for cancer treatment; however, their functionality and physiological role are still under investigation [40,63]. Moreover, stronger preclinical models (immunocompetent mice, humanized patient derived xenograft (PDX) models) to predict the human response to the treatment are needed for early phase clinical trials [58]. Additionally, a better understanding of EV biological function is needed, and several issues related to the purification, loading, targeting and scaling-up of EVs as DDS must be carefully considered to successfully transit these particles from bench to bedside [40,63,94].

**Author Contributions:** L.H.-O. drafted the work, P.G., S.S.J. revised the manuscript critically for important intellectual content and approved the final version, J.S.-F., F.A., D.R., I.A. made substantial contributions to conception and design of the review. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was partially supported by grant PI17/02242 and PI20/01474 from Fondo de Investigaciones Sanitarias (FIS) of Instituto Carlos III (ISCIII), co-financed by the European Regional Development Fund (FEDER) and the EvoNano project, and was funded by the European Union's Horizon 2020 FET Open programme under grant agreement No. 800983.

**Conflicts of Interest:** The authors declare no conflict of interest.

### **References**


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