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.

译文

:表皮生长因子受体(EGFR)在多种实体瘤中过表达。在这项研究中,我们利用高亲和力的EGFR拮抗抗体(ZEGFR)与负载阿霉素的聚乙二醇化脂质体(LS-Dox)结合,在体内外对EGFR A431肿瘤细胞进行被动和主动靶向。体外研究表明,在EGFR A431细胞中,Dox脂质体与ZEGFR(AS-Dox)的结合比LS-Dox表现出更高的Dox摄取,而在EGFR- B16F10细胞中则没有,而导致了选择性的细胞毒性。在体内,AS-Dox证实了其长的循环时间和在肿瘤中的有效积累。该靶向化学疗法实现了更大的肿瘤抑制。此外,这种低剂量但有效的靶向治疗降低了全身毒性,例如H&E染色证明了体重减轻和器官损伤。因此,选择性靶向LS-Dox并结合ZEGFR可增强抗肿瘤作用并改善全身安全性。这些结果表明,LS-Dox结合ZEGFR可能被开发为治疗EGFR肿瘤的潜在工具。

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