Biomimetic liposomal nanozymes improve breast cancer chemotherapy with enhanced penetration and alleviated hypoxia

BACKGROUND: 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, H(2)O(2)-rich conditions and condensed extracellular matrix in TME as well as low targeted ability. METHODS: We developed a nanosystem H-MnO(2)-Dox-Col NPs based on mesoporous manganese dioxide (H-MnO(2)) in which Dox was loaded in the core and collagenase (Col) was wrapped in the surface. Further the H-MnO(2)-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-MnO(2)-Dox-Col for in vitro and in vivo study. RESULTS: Our results shows that MP@H-MnO(2)-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. CONCLUSIONS: This multifunctional biomimetic nanodelivery system exhibited antitumor efficacy in vivo and in vitro, thus having potential for the treatment of breast cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-01874-7.