Polycarbonate Magnetic Microspheres Containing Tumor Necrosis Factor- α for Potential Targeted Hepatic Carcinoma Therapeutics

Polycarbonate copolymers poly(trimethylene carbonate-co-5,5-dimethyl trimethylene carbonate) (PC, P(TMC-co-DTC)) was synthesized by the polymerization of trimethylene carbonate (TMC) and 5,5-dimethyl trimethylene carbonate (DTC) using Tin (II) 2-ethylhexanoate (Sn(Oct)2) as a catalyst. The modified water-in-oil-in-water (w/o/w) solvent evaporation technique was adopted to produce anticancer magnetic polycarbonate microspheres TNF-PC-M containing human tumor necrosis factor-α (TNF) and Fe3O4 magnetic ultrafine powders. The experiments evidenced that these magnetic polycarbonate microspheres had the strong magnetic responsiveness and high TNF loading concentration. Drug release studies showed that the microspheres sustained a steady release rate of TNF in PBS in vitro for up to 55 days. In vitro cytotoxicity assays demonstrated the microspheres had the high inhibition and anti-tumor action to human hepatocellular carcinoma (Bel-7204) cells in vitro. In vivo site-specific therapy in nude mice bearing Bel-7204 indicated that the microspheres possessed a markedly high antitumor activity.