Targeted delivery of antitumor drugs is especially important for tumour therapy. Tumour targeting peptides have been shown to be very effective drug carriers for tumour therapy. Interleukin-4 receptor (IL-4R) is overexpressed on the surface of various human solid tumours. To obtain a better targeting peptide, we first designed a novel targeting peptide derived from interleukin-4 (IL-4), ILBP-b. ILBP-b contains the key high-affinity binding residue E9 of IL-4 to IL-4R. Compared with a reported targeting peptide ILBP-a (containing another key high affinity residue R88), ILBP-b was proved to be a better targeting peptide by the fluorescence experiments. Then, we further fused ILBP-b and ILBP-a to increase the multisite-binding ability of ILBP-b and got a better targeting peptide ILBP-ba. ILBP-ba showed a stronger preferential binding ability to IL-4R high-expressing cells than ILBP-a and ILBP-b. Competitive binding experiments demonstrated ILBP-ba specifically targets IL-4R. By fusing ILBP-ba with drug protein trichosanthin (TCS), in vitro drug carrying experiments showed that ILBP-ba could specifically enhance the killing effect of TCS on IL-4R high-expressing tumour cells (more than 10 folds). These results indicated that ILBP-ba has great potential for drug delivery applications targeting IL-4R and will be beneficial for the development of tumour therapeutic agents.
Keywords: Tumour-targeting peptide; drug delivery; interleukin-4; interleukin-4 receptor; trichosanthin (TCS).