Coupling EGFR-Antagonistic Affibody Enhanced Therapeutic Effects of Cisplatin Liposomes in EGFR-expressing Tumor Models.

Epidermal growth factor receptor (EGFR) is an efficient target for cancer therapy. In this study, a high-affinity EGFR-antagonistic affibody (Z EGFR) molecule coupled with cisplatin-loaded PEGylated liposomes (LS-DDP) was applied to actively target EGFR+ A431 tumor cells in vitro and in vivo. The LS-DDP coupled with Z EGFR (AS-DDP) had an average size of 140.01 ± 0.84 nm, low polydispersity, a zeta potential of -13.40 ± 0.8 mV, an acceptable encapsulation efficiency of 17.30 ± 1.35%, and released cisplatin in a slow-controlled manner. In vitro , AS-DDP demonstrated a higher amount of platinum intracellular uptake by A431 cells than LS-DDP. The IC50 value of AS-DDP (9.02 ± 1.55 μg/ml) was much lower than that of LS-DDP (16.44 ± 0.87 μg/ml), indicating that the anti-tumor effects of AS-DDP were remarkable due to the modification of Z EGFR. In vivo , the concentration of AS-DDP in the tumor site increased more than 1.76-fold, while an increase in apoptotic cells at 48 h compared to the LS-DDP was also observed, illustrating that AS-DDP possessed excellent tumor-targeting efficiency. As a result, the targeted nano-liposomes achieved greater tumor suppression. Therefore, selective targeting of LS-DDP coupled with Z EGFR enhanced the anti-tumor effects and appeared to be a promising strategy for the treatment of EGFR+ tumors. [ABSTRACT FROM AUTHOR]