Preparation and characteristics of magnetite‐labelled antibody with the use of poly(ethylene glycol) derivatives

With a view to the application of magnetic particles in cancer thermotherapy (hyperthermia), methods of preparing a bio‐applicable magnetite with targeting activity towards cancer cells were investigated, and the properties of the material examined. Poly(ethylene glycol) (PEG)‐magnetite consisting of magnetite (Fe3O4) and PEG with terminal carboxy or amino groups was prepared. Monoclonal antibody was then immobilized covalently on to the PEG‐magnetite. Among three different immobilization methods employed, the highest immobilization density of 492 mg of protein/g of PEG‐magnetite was achieved by using water‐soluble carbodi‐imide. However, with respect to residual antibody activity, only the method in which IgG sugar chains were oxidized to give aldehyde groups for coupling to N‐terminal PEG‐magnetite was satisfactory, with about 60% of the activity surviving. The immobilization density by this method (109 mg of protein/g of PEG‐magnetite) was also sufficiently high. The product, termed magnetite‐labelled antibody, was of sub‐micrometre size and showed easy magnetophoresis. It was further elucidated that cancer‐specific magnetite‐labelled antibody bound to cancer cells at an amount of 50 mg of magnetite/cm3 of cells. The PEG‐magnetite generates heat at an evolution rate of 31.5 W/g, and the amount adsorbed to the cells was calculated to be high enough to heat a tumour 1 cm in diameter to more than 42 degrees C in 30 s under an alternating magnetic field [at an intensity of 572 Oe (approx. 45.5 kA/m) and a frequency of 240 kHz]. This magnetite‐labelled antibody is expected to be applicable clinically as a therapeutic agent for the induction of hyperthermia. 1995 The Swiss Political Science Review