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Abstract
Objective: The specific expression of transferrin receptor can represent a diagnostic tool or therapeutic target in solid tumors expressing this antigen. Herein, the human transferrin receptor monoclonal antibody (T9) was investigated as a tumor-targeting group for active targeted-drug delivery systems.
Materials and methods: A tumor-targeted conjugate T9-TNF was synthesized by the attachment of both human transferrin receptor monoclonal antibody (T9) as a tumor-targeting group and human tumor necrosis factor-α (TNF) as an anti-cancer drug to two terminated hydroxyl groups of poly(ethylene glycol). Subsequently, a solvent evaporation technique was adopted to produce anti-cancer magnetic polymer microspheres T9-TNF-PC-M containing T9-TNF and Fe3O4 magnetic ultrafine powders (M) using poly(trimethylene carbonate-co-5,5-dimethyl trimethylene carbonate) (PC, P(TMC-co-DTC)) as a polymeric carrier.
Results and discussion: These magnetic polycarbonate microspheres possessed a steady TNF release rate in phosphate buffer saline solution, strong magnetic responsiveness and high T9-TNF loading capacity. In vitro cytotoxicity assays demonstrated the microspheres T9-TNF-PC-M and conjugate T9-TNF were strongly inhibitory to the human hepatic carcinoma (Bel-7204) cells. In vivo site-specific therapy in nude mice with human hepatic carcinoma indicated that the microspheres T9-TNF-PC-M and conjugate T9-TNF possessed markedly higher anti-tumor activity against Bel-7204 in mice than that of TNF.
Conclusions: These results indicated that the magnetic polycarbonate microspheres were suitable as the potential-targeted treatment for hepatic carcinoma therapeutics.