Efficient Liposome Loading onto Surface of Mesenchymal Stem Cells via Electrostatic Interactions for Tumor-Targeted Drug Delivery.

Mesenchymal stem cells (MSCs) have a tumor-homing capacity; therefore, MSCs are a promising drug delivery carrier for cancer therapy. To maintain the viability and activity of MSCs, anti-cancer drugs are preferably loaded on the surface of MSCs, rather than directly introduced into MSCs. In this study, we attempted to load liposomes on the surface of MSCs by using the magnetic anionic liposome/atelocollagen complexes that we previously developed and assessed the characters of liposome-loaded MSCs as drug carriers. We observed that large-sized magnetic anionic liposome/atelocollagen complexes were abundantly associated with MSCs via electrostatic interactions under a magnetic field, and its cellular internalization was lower than that of the small-sized complexes. Moreover, the complexes with higher atelocollagen concentrations showed lower cellular internalization than the complexes with lower atelocollagen concentrations. Based on these results, we succeeded in the efficient loading of liposomes on the surface of MSCs by using large-sized magnetic anionic liposomes complexed with a high concentration of atelocollagen. The constructed liposome-loaded MSCs showed a comparable proliferation rate and differentiation potential to non-loaded MSCs. Furthermore, the liposome-loaded MSCs efficiently adhered to vascular endothelial cells and migrated toward the conditioned medium from cancer cells in vitro and solid tumor tissue in vivo. These findings suggest that liposome-loaded MSCs could serve as an efficient cell-based drug carrier for tumor-targeted delivery.