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  • Title: Increasing the antitumor efficacy of doxorubicin liposomes with coupling an anti-EGFR affibody in EGFR-expressing tumor models.
    Author: Jia D, Yang Y, Yuan F, Fan Q, Wang F, Huang Y, Song H, Hu P, Wang R, Li G, Liu R, Li J.
    Journal: Int J Pharm; 2020 Aug 30; 586():119541. PubMed ID: 32544521.
    Abstract:
    Epidermal growth factor receptor (EGFR) is overexpressed in a wide range of solid tumors. In this study, we exploited a high-affinity EGFR-antagonistic affibody (ZEGFR) coupled to a doxorubicin loaded pegylated liposome (LS-Dox) for concurrent passive and active targeting of EGFR+ A431 tumor cells in vitro and in vivo. The in vitro studies revealed that the Dox liposomes coupled with ZEGFR (AS-Dox) showed a higher Dox uptake than LS-Dox in EGFR+ A431 cells but not in EGFR- B16F10 cells, resulting in a selectively enhanced cytotoxicity. In vivo, AS-Dox confirmed its long circulation time and efficient accumulation in tumors. This targeted chemotherapy achieved greater tumor suppression. Further, this low-dose but effective targeted treatment reduced systemic toxicity such as body weight loss and organ injury demonstrated by H&E staining. Thus, selective targeting of LS-Dox coupled with ZEGFR enhanced antitumor effects and improved systemic safety. These results demonstrated that LS-Dox coupled with ZEGFR might be developed as a potential tool for therapy of EGFR+ tumors.
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