HB-EGF as a targeted carrier for drug delivery in some cancers

Cell-penetrating peptides (CPPs) facilitate efficient biomolecule delivery with low immunogenicity and cytotoxicity, making them ideal for in vivo drug delivery. Heparin-binding epidermal growth factorlike growth factor (HB-EGF), a ligand of the epidermal growth factor receptor (EGFR), is overexpressed in tumors and can promote angiogenesis. Doxorubicin (DOX), a chemotherapeutic, treats various cancers but has limited use with HB-EGF as a carrier. Aim. In this study we focused on the HB-EGF's potential in enhancing DOX delivery and antitumor effects. Methods. Recombinant sHB-EGF was expressed in E. coli, purified by IMAC, and loaded with DOX with further dialysis of the complex from unbound antibiotics. Binding to cell surfaces (A431, 3T3, Vero), as well as ROS production using DCFH-DA, were analyzed by flow cytometry. Cell viability was assessed with MTT assays after 48 h. Results. sHB-EGF fluorescent derivatives effectively bound to A431 cells, enhancing DOX delivery to squamous-cell carcinoma and significantly reducing cell viability. Conclusions. HB-EGF efficiently delivers DOX into cells, suggesting its potential as a targeted drug carrier for EGFR/ErbB-1 overexpressed cancers.