An epidermal growth factor (EGF) conjugate, with potential for selective delivery of DNA-binding compounds to malignancies overexpressing the EGF receptor, is presented. The development of a two-step targeting principle implies that, after cellular binding and internalisation, the conjugate should be degraded and the released toxic agents should be in such chemical forms that they bind to the cellular DNA. Boronated compounds with proved DNA-intercalation, earlier developed for boron neutron capture therapy, could be most suitable as the toxic agents. In this study the amino terminus of I-125-EGF was coupled to the 5' end of double stranded DNA, constructed of a 30-mer self-complementary oligonucleotide, to generate a I-125-EGF-DNA conjugate. Binding, internalisation and retention of the conjugate were investigated in vitro on human glioma cells overexpressing the EGF receptor. The generated I-125-EGF-DNA conjugate was shown to bind specifically to the EGF receptor. The conjugate was thereafter internalised and degraded efficiently. The results indicate that the I-125-EGF-DNA conjugate has suitable biological properties for the planned tests of selective delivery of DNA-binding toxic compounds in a two-step targeting process.

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