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Development of Tumor Targeting Magnetic Nanoparticles for Cancer Therapy

R. Ivkov, S.J. DeNardo, L.A. Miers, A. Natarajan, A.R. Foreman, C. Gruettner, G.N. Adamson and G.L. DeNardo
Triton BioSystems, Inc., US

cancer, immunotherapy, magnetic nanoparticles, antibodies, thermotherapy

111In-ChL6 MAb-linked iron oxide nanoparticles (bioprobes) pharmacokinetics, tumor uptake and the therapeutic effect of inductively heating these bioprobes by an externally applied AMF were studied in athymic mice bearing human breast cancer HBT3477 xenografts. Bioprobe doses (20mg/2.2mg ChL6/ bioprobe), were administered i.v. with 50μg ChL6; a 153 kHz AMF was given 72 hr post injection (pi) for therapy with amplitudes of 1,300, 1,000 or 700 Oersteds. Weights, blood counts and tumor size were monitored and compared with control mice receiving nothing, or AMF or bioprobes alone. 111In-ChL6 bioprobe binding in vitro to HBT3477 cells was 50 to 70% of that of 111In-ChL6. At 48 hours, tumor, lung, kidney, and marrow uptake of the 111In-ChL6 bioprobes were not different from that observed in prior studies of 111In-ChL6. Significant therapeutic responses from AMF/bioprobe therapy were demonstrated. Toxicity was only seen in the 1,300 Oe AMF cohort, with 4 of 12 immediate deaths and skin erythema. Electron micrographs showed bioprobes on the surfaces of the HBT3477 cells of excised tumors and tumor necrosis 24 hours after AMF/bioprobe therapy. This study shows that mAb-conjugated nanoparticles (bioprobes), when given i.v., escape into the extravascular space and bind to cancer cell membrane antigen, so that bioprobes can be used in concert with externally applied AMF to deliver thermoablative cancer therapy.

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