Selective targeting of magnetic albumin microspheres to the Yoshida sarcoma: Ultrastructural evaluation of microsphere disposition

Abstract

Magnetic albumin microspheres (1 μ m average diameter) were selectively targeted to subcutaneous solid Yoshida sarcoma tumors (average size 450 mm 2) in Holtzman rats. This was accomplished by placing an external magnet adjacent to the tumor while the microspheres were infused. Microspheres contained ultra-fine particles of Fe 3O 4 and no drug (placebo). Placebo microspheres were used due to the previously demonstrated rapid tumoricidal effect of targeted low-dose doxorubicin microspheres. Animals were killed 10 min, 60 min, 30 min, 24 hr and 72 hr after microsphere administration and tumors were examined by transmission electron microscopy to determine the in vivo disposition of the magnetically targeted microspheres. Using placebo microspheres, we have demonstrated microspheres endocytosed in endothelial cells as early as 10 min after infusion. By 30 min microspheres can be seen in the extravascular compartment, sitting adjacent to tumor cells and occasionally in tumor cells. By 24 hr the majority of microspheres have been endocytosed by tumor cells. Microspheres were still observed within tumor cells as late as 72 hr after administration. The rapid extravasation and cellular uptake of magnetically focused microspheres explains the extremely rapid tumoricidal effect previously observed when doxorubicin-containing microspheres were targeted to the tumor.