Bi-Functional Radiotheranostics of 188Re-Liposome-Fcy-hEGF for Radio- and Chemo-Therapy of EGFR-Overexpressing Cancer Cells

Epidermal growth factor receptor (EGFR) specific therapeutics is of great importance in cancer treatment. Fcy-hEGF fusion protein, composed of yeast cytosine deaminase (Fcy) and human EGF (hEGF), is capable of binding to EGFR and enzymatically convert 5-fluorocytosine (5-FC) to 1000-fold toxic 5-fluorocuracil (5-FU), thereby inhibiting the growth of EGFR-expressing tumor cells. To develop EGFR-specific therapy, ¹⁸⁸Re-liposome-Fcy-hEGF was constructed by insertion of Fcy-hEGF fusion protein onto the surface of liposomes encapsulating of ¹⁸⁸Re. Western blotting, MALDI-TOF, column size exclusion and flow cytometry were used to confirm the conjugation and bio-activity of ¹⁸⁸Re-liposome-Fcy-hEGF. Cell lines with EGFR expression were subjected to treat with ¹⁸⁸Re-liposome-Fcy-hEGF/5-FC in the presence of 5-FC. The ¹⁸⁸Re-liposome-Fcy-hEGF/5-FC revealed a better cytotoxic effect for cancer cells than the treatment of liposome-Fcy-hEGF/5-FC or ¹⁸⁸Re-liposome-Fcy-hEGF alone. The therapeutics has radio- and chemo-toxicity simultaneously and specifically target to EGFR-expression tumor cells, thereby achieving synergistic anticancer activity.