Abstract
This study was undertaken to evaluate feasibility of metal coordination as a method to prepare a protein drug-polymer conjugate. A metal chelating, diethylenetriaminepentaacetic acid (DTPA) residue was introduced to a polysaccharide, dextarn for metal coordination. Recombinant human tumor necrosis factor α(TNF) was used as a protein drug. A simple mixing with the DTPA-dextran in an aqueous solution containing Cu2+ enabled TNF to coordinately conjugate to dextran. Following intravenous (i.v.) injection into tumor-bearing mice, the TNF-DTPA-Dextran conjugate exhibited a significantly higher tumor accumulation of TNF and the longer retention period than free TNF or its mixture with the DTPA-dextran. I. V. injection of the TNF-DTPA-dextran conjugate suppressed tumor growth to a significantly greater extent than that of free TNF even at a lower injection dose. We concluded that dextran conjugation based on Cu2+ coordination was a promising way to enhance the antitumor effect of TNF as a result of its passive tumor targeting.
