Liposome-Loaded Mesenchymal Stem Cells Enhance Tumor Accumulation and Anti-Tumor Efficacy of Doxorubicin in Mouse Tumor Models of Melanoma.

Background

Mesenchymal stem cells (MSCs) possess an intrinsic tumor-tropic ability, and therefore, MSCs may potentially be used as biomimetic carriers for active drug delivery systems targeting tumors. We previously developed a method to efficiently load liposomes onto the surface of MSCs via electrostatic interactions. The prepared liposome-loaded MSCs (Lip-MSCs) spontaneously accumulated in solid melanoma tumors with low vascular permeability while stably carrying liposomes.

Methods

To explore Lip-MSC applications in cancer chemotherapy, doxorubicin (DOX)-encapsulated liposomes (DOX-Lip) were prepared and loaded onto MSCs. The cell viability, DOX-releasing properties, tumor-homing capacity, and anti-tumor efficacy of DOX-Lip-MSCs were analyzed.

Results

Small liposomes (100 nm) retained DOX, whereas significant leakage of DOX was observed from 600 nm-sized liposomes. Based on this result, we used 100 nm DOX-Lip for the preparation of DOX-Lip-MSCs. Compared with MSCs loaded with DOX by incubation with DOX solution, DOX-Lip-MSCs could load a larger amount of DOX with minimal cytotoxicity. DOX-Lip-MSCs also showed sustained DOX release. DOX-Lip-MSCs efficiently migrated toward the conditioned medium of B16/BL6 melanoma cells in vitro and accumulated in B16/BL6 tumors in vivo, leading to a significant inhibitory effect on tumor growth.

Conclusions

Lip-MSCs can serve as an efficient carrier to deliver anti-cancer drugs into solid tumors.