Calcium phosphate particles stimulate exosome secretion from phagocytes for the enhancement of drug delivery

Exosomes are attractive potential carriers for drug delivery because of their natural function of transferring biomolecules among cells without eliciting immune responses. However, an obstacle to the application of exosomes for drug delivery is the difficulty in collecting sufficient numbers of these vesicles. In this study, we demonstrate treatment with calcium phosphate (CaP) particles could increase over two-fold the number of exosomes secreted from macrophage-like RAW264.7 cells and monocyte-like THP-1 cells. CaP particles were easily internalized into cells and dissolved in acidic late-endosomes or lysosomes, resulting in the rupture of their membranes followed by the release of Ca²⁺ into cytosol. Moreover, we found that exosomes secreted from cells treated with CaP particles are not contaminated by the Ca²⁺ released from CaP; the Ca²⁺ contents in exosomes secreted from CaP particle-treated cells were similar to that in exosomes from untreated control cells. This study highlights the potential for the efficient production of exosomes using CaP particles for drug delivery.