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Updated: Feb 16, 2026
Construction of Cyclic Cell-Penetrating Peptides for Enhanced Penetration of Biological Barriers
Published on: September 19, 2022
Structure optimisation to improve the delivery efficiency and cell selectivity of a tumour-targeting cell-penetrating
Xue-Wei Cao1, Xu-Zhong Yang2, Xuan Du1
1a State Key Laboratory of Bioreactor Engineering , East China University of Science and Technology , Shanghai , PR China.
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.
Insights
A novel tumor-targeting cell-penetrating peptide (TCPP), EHB, enhances drug delivery into cancer cells. EHB shows superior transmembrane ability and tumor cell selectivity, improving anti-cancer drug efficacy and safety.
Area of Science:
- Biotechnology
- Cancer Therapy
- Drug Delivery
Background:
- Cell-penetrating peptides (CPPs) facilitate biomacromolecule transport across cell membranes but lack tumor selectivity in cancer therapy.
- Epidermal growth factor receptor (EGFR) is a validated target in clinical cancer therapy.
Purpose of the Study:
- To develop a novel tumor-targeting cell-penetrating peptide (TCPP) with enhanced cell selectivity and transmembrane ability for cancer therapy.
- To evaluate the efficacy of the novel TCPP, EHB, in delivering anticancer agents into EGFR-overexpressing cancer cells.
Main Methods:
- Engineered a novel TCPP, EHB (ELBD-C6H), by incorporating an alpha helix structure into a vaccinia growth factor (VGF)-derived amino acid sequence and fusing it with a heparin-binding epidermal growth factor-like growth factor (HB-EGF)-derived heparin-binding domain (C6H).
- Assessed the transmembrane ability and tumor cell selectivity of EHB compared to S3-HBD and the classic CPP TAT.
- Investigated the ability of EHB to deliver the anticancer protein MAP30 into EGFR-overexpressing cancer cells and its effect on normal cells.
Main Results:
- EHB demonstrated significantly higher transmembrane ability (20-fold) and tumor cell selectivity (3000-fold) compared to S3-HBD and TAT.
- EHB successfully delivered the anticancer protein MAP30 into EGFR-overexpressing cancer cells, inhibiting cell growth.
- EHB exhibited greatly reduced interaction with normal cells, indicating high specificity.
Conclusions:
- EHB represents a novel and efficient TCPP for the targeted delivery of therapeutic molecules into cancer cells.
- The enhanced selectivity and delivery capability of EHB hold promise for improving the efficacy and safety of anti-cancer drugs.
- This TCPP has potential applications in targeted cancer therapy by selectively delivering drugs to tumors.
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