Locoregional cancer treatment with magnetic drug targeting

The specific delivery of chemotherapeutic agents to their desired targets w ith a minimum of systemic side effects is an important, ongoing challenge o f chemotherapy, One approach, developed in the past to address this problem , is the i.v. injection of magnetic particles [ferrofluids (FFs)] bound to anticancer agents that are then concentrated in the desired area (e.g., the tumor) by an external magnetic field. In the present study, we treated squ amous cell carcinoma in rabbits with FFs bound to mitoxantrone (FF-MTX) tha t was concentrated with a magnetic field. Experimental VX-2 squamous cell c arcinoma was implanted in the median portion of the hind limb of New Zealan d White rabbits (n = 26), When the tumor had reached a volume of similar to 3500 mm(3), FF-MTX was injected intraarterially (i.a.; femoral artery) or i.v. (ear vein), whereas an external magnetic field was focused on the tumo r. FF-MTX i.a. application with the external magnetic field resulted in a s ignificant (P < 0.05), complete, and permanent remission of the squamous ce ll carcinoma compared with the control group (no treatment) and the i.v. FF -MTX group, with no signs of toxicity. The intratumoral accumulation of FFs was visualized both histologically and by magnetic resonance imaging. Thus , our data show that i.a. application of FF-MTX is successful in treating e xperimental squamous cell carcinoma. This "magnetic drug targeting" offers a unique opportunity to treat malignant tumors locoregionally without syste mic toxicity. Furthermore, it may be possible to use these magnetic particl es as a "carrier system" for a variety of anticancer agents, e.g., radionuc lides, cancer-specific antibodies, and genes.