Exosome Heterogeneity Affects the Distal “Barrier-Crossing” Trafficking of Exosome Encapsulated Quantum Dots

The biological activities of nanoparticles
(NPs), which
include
endocytosis by macrophages and subsequent intracellular degradation
and/or release, transfer to other cells, or translocation across tissue
barriers, highly depend on their fate in living organisms. Yet, translocation
across barriers, especially the distal “barrier-crossing”
trafficking of NPs, is still unclear. The exosome (Exo) plays a crucial
role in intercellular communication and biological barrier trafficking.
Here, we report that ZnCdSe@ZnS quantum dots (QDs), as a representation
of NPs in biomedical applications, could cross the blood-brain barrier
and approach the mouse brain via active Exo encapsulation. By employing
multiple techniques, we demonstrated that QDs were internalized by
macrophages (J774A.1) and tumor cells (HeLa) and then released to
the extracellular environment along with Exo. Exo encapsulation facilitates
the distal barrier-crossing trafficking of QDs in vivo, while Exo biogenesis inhibitor GW4869 suppressed the QDs enriched
in the brains of mice with a 4T1-Luc breast cancer xenograft. Interestingly,
Exo heterogeneity affects the distal trafficking of enveloped QDs.
Exo derived from tumorous HeLa cells, not macrophages, that were enriched
in functional proteins with cell adhesion, cell migration, axon guidance,
and cell motility, showed a better capacity for the remote trafficking
of QDs. This study proposes Exo as a vehicle to deliver exogenous
NPs to translocate across the distal barrier and provides further
information for biomedical application and the risk assessment of
NPs.