Tumor remission in Yoshida sarcoma-bearing rts by selective targeting of magnetic albumin microspheres containing doxorubicin.

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Abstract
Magnetically responsive albumin microspheres containing doxorubicin and magnetite (Fe3O4) were selectively targeted to [rat] Yoshida sarcoma tumor cells in rats by utilizing an extracorporeal magnet. Tumor cells were incoinoculated s.c. in the tail of rats; the tumors initiating treatment. Drug-bearing microspheres (0.5 mg of doxorubicin per kg of body weight) were infused approximal to the tumor through the ventral caudal artery while the tumor was exposed to an external magnetic field of 5500 Oe (Oersted] for 30 min. Control animals received free doxorubicin administered i.v. (5 mg/kg) or infused intraarterially (5 and 0.5 mg/kg), drug-bearing microspheres infused intraarterially (0.5 mg/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 3 rats; no deaths or metastases occurred in the experimental group. Significant increases in tumor size with widespread metastases occurred in all control groups; most rats died. 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.