Multifunctional Hybrid Membrane-Coated Nanomotors for Magnetically Guided, Cascade-Activated Chemoimmunotherapy for Triple-Negative Breast Cancer

Here, we report a multifunctional hybrid membrane-coated nanomotor for cancer chemoimmunotherapy, which consists of mesoporous silica-coated iron oxide nanoparticles (MF) as a drug carrier, loaded with doxorubicin (DOX), l-arginine (l-arg), and glucose oxidase (GOx), and camouflaged with a hybrid of red blood cell membranes (mRBC) and cancer cell membranes (CCM). RM-GDL-MF has a cascade of catalytic reactions, where glucose is catalyzed by GOx to produce H₂O₂, and l-arg is oxidized by the produced H₂O₂ to release nitric oxide (NO), leading to self-propelled motion in order to promote the penetration of the extracellular matrix (ECM) in the tumor. The hybrid membrane provides not only stealth properties from mRBC to evade immune clearance but also tumor-orientation ability to target the tumor from the CCM. The generation of reactive oxygen species (ROS) was demonstrated to induce immunogenic cell death (ICD), thereby enhancing antitumor immune responses through the recruitment of CD8⁺ tumor-infiltrating lymphocytes (TILs), promotion of dendritic cell maturation, and reprogramming of macrophages toward the proinflammatory M1 phenotype. <i>In vitro</i> and <i>in vivo</i> experiments demonstrated that RM/R4-GDL-MF had significant tumor accumulation efficiency and antitumor efficacy. This multimodal nanomotor shows great potential for effectively treating tumors.