Structure optimisation to improve the delivery efficiency and cell selectivity of a tumour-targeting cell-penetrating peptide

Abstract

Cell-penetrating peptide (CPP) is used for the delivery of biomacromolecules across the cell membrane and is limited in cancer therapy due to the lack of cell selectivity. Epidermal growth factor receptor (EGFR) has been widely used in clinical targeted therapy for tumours. Here, we reported a novel tumour targeting cell-penetrating peptide (TCPP), EHB (ELBD-C6H) with 20-fold and 3000-fold greater transmembrane ability and tumour cell selectivity than our previously reported S3-HBD and classic CPP TAT, respectively. In this new TCPP, a specific alpha helix structure was inserted into a repeated amino acid (AA) sequence formed by tandem multiple selected key AA residues of vaccinia growth factor (VGF), and this sequence was then fused to a tailored heparin binding domain sequence (C6H) derived from heparin-binding epidermal growth factor-like growth factor to intensify its targeting delivery ability. EHB could carry anticancer proteins such as MAP30 (Momordica Antiviral Protein 30 kDa) into EGFR-overexpressing cancer cell and inhibit cell growth, but it had a greatly reduced interaction with normal cells. These results indicated that EHB, as a novel efficient TCPP for the selective delivery of drug molecules into cancer cells, would help to improve the efficacy and safety of anti-tumour drugs.

Keywords:

• Tumour targeting cell-penetrating peptide (TCPP)
• epidermal growth factor receptor (EGFR)
• EGFR binding domain
• heparin-binding domain (HBD)

Disclosure statement

The authors declare that they have no conflicts of interest regarding the conduct or outcomes of this study.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Grant No. 81571795].