Hyaluronan decoration of milk exosomes directs tumor-specific delivery of doxorubicin.

Milk exosomes (mExo), similar to cell-derived exosomes, are emerging as promising nanocarriers for delivery of therapeutic molecules such as chemical drugs and siRNA, due to the excellent biocompatibility and low-cost production from bovine milk. However, additional modification remains required to apply milk exosomes for tumor-specific drug delivery. Here, we attempted to develop a novel strategy for directing doxorubicin (Dox)-loaded mExo to CD44-overexpressing tumor cells. Hyaluronan (HA), a CD44-specific ligand, was functionalized with an amphiphilic molecule DSPE-PEG2000, which enabled the spontaneous decoration of Dox-loaded mExo with HA onto the phospholipid bilayer. The obtained nanocarrier HA-mExo-Dox was shown to be able to selectively deliver Dox into cells with over-expressed CD44 instead of control cells and trigger the notable tumor cells death in the in vitro analysis. This study demonstrates the potential use of HA-displaying mExo for tumor cell-specific drug delivery and this strategy should prove to be feasible for targeted cancer therapy.