Assessment of a novel nanoparticle hyperthermia therapy in a murine model of osteosarcoma

Abstract

Objective: To evaluate the effects of nanoparticle hyperthermia therapy on monocyte function and tumor-derived factors associated with macrophage polarization in a murine osteosarcoma model.

Study design: Experimental study.

Animals: Female C3H mice.

Methods: Peripheral blood monocyte cell surface phenotype, monocyte chemotaxis, tumor messenger RNA expression, and survival were compared among osteosarcoma (OS)-bearing mice treated with nanoparticle hyperthermia therapy, OS-bearing mice with osteomyelitis, OS-bearing mice, vehicle control mice, and normal control mice.

Results: OS-bearing mice with osteomyelitis had a higher proportion of "nonclassical" monocytes (Ly6C^lo ) compared with all other experimental groups. There were alterations in monocyte expression of multiple chemokine receptors among experimental groups including CXCR2, CCR2, and CXCR4. Monocytes from OS-bearing mice treated with hyperthermia therapy exhibited greater chemotaxis compared with monocytes from OS-bearing mice with osteomyelitis.

Conclusion: OS likely induced alterations in monocyte phenotype and function. Nanoparticle hyperthermia therapy increased in vitro monocyte chemotaxis.

Clinical impact: Enhancing monocyte/macrophage function in dogs with OS may enhance antitumor immunity.