Doxorubicin（Dox）已被临床指南推荐为乳腺癌标准护理治疗。然而，Dox治疗面临挑战，例如TME中的缺氧，酸中毒，H2O2丰富的条件和压缩的细胞外基质，以及低靶向能力。我们基于介孔二氧化锰（H-MnO2）开发了一种纳米系统H-MnO2-Dox-Col NPs，其中Dox被加载在核心中，胶原酶（Col）包裹在表面上。进一步，H-MnO2-Dox-Col NPs被炎症靶向RAW264.7细胞膜和pH敏感的脂质体覆盖成仿生膜（MP）形成仿生MP@H-MnO2-Dox-Col进行体外和体内研究。我们的结果表明，MP@H-MnO2-Dox-Col能够增强Dox的作用，具有低的心毒性，基于肿瘤组织中的有效穿透，缓解TME中的缺氧，pH敏感的药物释放以及Dox的靶向传递的多功能。这种多功能仿生纳米递送系统在体内和体外表现出抗肿瘤疗效，因此具有治疗乳腺癌的潜力。©2023作者。

Doxorubicin (Dox) has been recommended in clinical guidelines for the standard-of-care treatment of breast cancer. However, Dox therapy faces challenges such as hypoxia, acidosis, H2O2-rich conditions and condensed extracellular matrix in TME as well as low targeted ability.We developed a nanosystem H-MnO2-Dox-Col NPs based on mesoporous manganese dioxide (H-MnO2) in which Dox was loaded in the core and collagenase (Col) was wrapped in the surface. Further the H-MnO2-Dox-Col NPs were covered by a fusion membrane (MP) of inflammation-targeted RAW264.7 cell membrane and pH-sensitive liposomes to form biomimetic MP@H-MnO2-Dox-Col for in vitro and in vivo study.Our results shows that MP@H-MnO2-Dox-Col can increase the Dox effect with low cardiotoxicity based on multi-functions of effective penetration in tumor tissue, alleviating hypoxia in TME, pH sensitive drug release as well as targeted delivery of Dox.This multifunctional biomimetic nanodelivery system exhibited antitumor efficacy in vivo and in vitro, thus having potential for the treatment of breast cancer.© 2023. The Author(s).