Constructing a better binding peptide for drug delivery targeting the interleukin-4 receptor.
J Drug Target
; 28(9): 970-981, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-32363946
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Péptidos
/
Unión Proteica
/
Tricosantina
/
Receptores de Interleucina-4
/
Antineoplásicos Fitogénicos
Límite:
Humans
Idioma:
En
Revista:
J Drug Target
Asunto de la revista:
FARMACOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China