表皮生长因子受体（EGFR）是三阴性乳腺癌（TNBC）的一个有前途的治疗靶点。最近，基于特定EGFR靶向肽GE11的纳米传递系统因其化学多功能性和良好的靶向能力而显示出优异的潜力。然而，在与GE11结合后EGFR下游的进一步研究尚未被探索。因此，我们通过使用双亲分子硬脂酸修饰GE11来量身设计了一种自组装纳米平台，名为GENP。在装载阿霉素（DOX）后，所得到的纳米平台GENP@DOX显示出高的装载效率和持续的药物释放。重要的是，我们的研究结果证明，GENP单独通过EGFR下游PI3K/AKT信号通路显著抑制MDA-MB-231细胞的增殖，有助于其DOX释放的协同治疗。进一步的工作表明，在最小毒性情况下，在正位TNBC和其骨转移模型中具有显著的治疗效果。总之，研究结果突显出我们的GENP功能化纳米平台是针对EGFR过度表达的癌症的协同治疗效果的一个有前途的策略。版权所有©2023 Elsevier Inc.发布。

Epidermal Growth Factor Receptor (EGFR) is a promising therapeutic target for triple-negative breast cancer (TNBC). Recently, specific EGFR-targeting peptide GE11-based delivery nano-system shows excellent potential because of its chemical versatility and good targeting ability. However, no further research focusing on the downstream of EGFR after binding with GE11 was explored. Hence, we tailor-designed a self-assembled nanoplatform named GENP using amphiphilic molecule of stearic acid-modified GE11. After loading doxorubicin (DOX), the resulted nanoplatform GENP@DOX demonstrated high loading efficiency and sustainable drug release. Importantly, our findings proved that GENP alone significantly suppressed the proliferation of MDA-MB-231 cells via EGFR-downstream PI3K/AKT signaling pathways, contributing to the synergistic treatment with its DOX release. Further work illustrated remarkable therapeutic efficacy both in orthotopic TNBC and its bone metastasis models with minimal biotoxicity. Together, the results highlight that our GENP-functionalized nanoplatform is a promising strategy for the synergistic therapeutic efficacy targeting EGFR-overexpressed cancer.Copyright © 2023. Published by Elsevier Inc.