Extracellular Vesicles: A Conduit for Nanomaterial to Travel into Solid Tumors

Nanomedicine translation is limited by inefficient delivery into solid tissues of multilayered cells such as tumors. Recently, several studies highlighted the importance of transcellular transport in nanoparticle (NP) extravasation into solid tumors. However, the underlying mechanism, especially the process from NP export from one cell and re-entry into another (termed "intercellular exchange" collectively), remains poorly understood. This review summarizes the progress in eliciting the NP transport across multilayered cells, and the efforts in studying the intercellular exchange of NPs. Particularly, our studies have revealed extracellular vesicles (EVs) as a novel conduit of NP transfer between cells in vitro and NP delivery into solid tumors in vivo. We further overviewed the efforts on how to chemically regulate this EV route for boosting the NP delivery efficiency. Overall, this review highlights the importance of EVs in NP delivery and provides new insights on enhancing nanomedicine efficacy through regulating EV machinery.