Gd@C82(OH)22 nanoparticles constrain macrophages migration into tumor tissue to prevent metastasis

Macrophages can be recruited to tumor tissues and play a supportive role in the invasion microenvironment. Since nanoparticles can be easily endocytosed by this kind of cell, the advances in nanotechnology offer a new sight to target macrophages in tumor tissues for diminishing harmful phenotypes. In the xenograft mouse model, we found that metallofullerol Gd@C82(OH)22 can not only reduced the macrophage density in the tumor tissue, but also decreased the expression of matrix metalloproteinase-9 produced by this kind of cell. To verify the phenomenon, a macrophage cell line, RAW264.7 was employed in the experiment, in vivo. Gd@C82(OH)22 nanoparticles can be engulfed by macrophages and the quantity was measured by inductively coupled plasma mass spectrometry. Fluorescent staining result showed that the particle induced the cells to adopt an elongated spindle morphology. The morphology alteration implied that the cells undergo mesenchymal migration, which is assisted by matrix metalloproteinase-9 to break down the extracellular matrix. But the reverse transcription PCR and western blots results indicated that the expression of matrix metalloproteinase-9 was reduced after the treatment of Gd@C82(OH)22. Thus, transwell migration assay indicated that macrophages were constrained to migrate through the collagen matrix.