Tumor cell targeting of transferrin-PEG-TNF-α conjugate via receptor mediated delivery

摘要

Transferrin (Tf) has been proposed to be a useful targeting agent to cancer cells. The aim of this study was to modify PEGylated recombinant human tumor necrosis factor alpha (PEG-TNF-α) with Tf to form Tf-PEG-TNF-α conjugate, which would maintain the advantages of PEGylation and also achieve the function of active targeting to tumor cells. The PEG-TNF-α conjugates with different PEGylation degree were synthesized and the reaction conditions were optimized in terms of the initial TNF-α:PEG molar ratios and reaction time. Tf was conjugated to the distal end of PEG-TNF-α after thiolation, the resulting Tf-PEG-TNF-α conjugate after purification with a perfusion chromatography technique contained approximately one Tf ligand on one TNF-α molecule. Two types of tumor cells, K562 and KB, were selected to assess the specificity and affinity of the conjugate to transferrin receptor (TfR). The results demonstrated that the Tf-PEG-TNF-α conjugate as well as Tf was bound specifically to the TfR on tumor cell surface and the affinity of Tf-PEG-TNF-α to TfR was similar to that of native Tf.