Magnetically responsive
albumin microspheres containing
doxorubicin and
magnetite (Fe3O4) were selectively targeted to
Yoshida sarcoma tumors in rats by utilizing an extracorporeal magnet.
Tumor cells were inoculated subcutaneously in the tail of rats, and the
tumors were allowed to grow to an average size of 9 X 45 mm prior to initiating treatment.
Drug-bearing
microspheres (0.5 mg of
doxorubicin per kg of
body weight) were infused proximal to the
tumor through the ventral caudal artery while the
tumor was exposed to an external magnetic field of 5500 Oe for 30 min. Control animals received free
doxorubicin administered either intravenously (5 mg/kg) or infused intraarterially (5 and 0.5 mg/kg),
drug-bearing
microspheres infused intraarterially (0.5mg/kg), without the external magnet, or placebo
microspheres with magnetic localization. Of the 12 animals treated with a single dose in the experimental group, 9 exhibited total remission of the
tumor, representing a disappearance of
tumors as large as 60 mm in length. Marked
tumor regression was observed in the remaining three rats, and no deaths or
metastases occurred in the experimental group. In contrast, significant increases in
tumor size with widespread
metastases occurred in all control groups and most rats died. These experiments indicate that targeting of oncolytic agents to solid
neoplasms by magnetic
microspheres may be a means of increasing the efficacy and decreasing the toxicity of
antitumor agents.