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  • Title: [Targeting chemotherapy with transferrin-neocarzinostatin conjugate].
    Author: Kohgo Y, Kato J, Sasaki K, Kondo H.
    Journal: Gan To Kagaku Ryoho; 1988 Apr; 15(4 Pt 2-1):1072-6. PubMed ID: 2968779.
    Abstract:
    In efforts to obtain preferential uptake of anticancer agents into tumors, we explored the possibility of delivering such agents by transferrin receptor-mediated endocytosis. Human diferric transferrin was conjugated with neocarzinostatin (NCS) using N-succinimidyl 3-(2-pyridyldithio)-propionate. This conjugate is capable of binding to the transferrin receptor and is internalized by endocytosis. The inhibitory effect of the conjugate on cell growth was remarkable when a human colorectal cancer cell line, M7609 was used as a target in vitro. In addition, in vivo efficacy of the conjugate in inhibiting the growth of M7609 cells implanted subcutaneously into nude mice was also observed when the conjugate was administered through a tail vein. The observed toxicity was a transient decrease in the red blood cell count, which returned to normal within 14 days. The half disappearance time of the conjugate was 55 min, while that of free NCS was 7 min. No serious side effects with regard to liver or kidney function were detected. This conjugate is an appropriate model for the receptor-mediated delivery of ligand-drug complex and may be useful for future clinical application.
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