Breast cancer-targeted therapy and doxorubicin multidrug resistance are reversed via macrophage membrane-camouflaged liposomes

Abstract

Medication therapy is the primary treatment for breast cancer. However, many patients develop multidrug resistance (MDR), which complicates treatment and reduces its effectiveness. To address this, a novel approach was developed by combining the chemotherapeutic drug, doxorubicin (DOX), and the MDR reversal agent, tetrandrine (Tet), within degradable liposomes covered with macrophage membranes to create MM@DOX-Tet nanoparticles (NPs). These NPs effectively reversed MDR in breast cancer cells, with an eight-fold increase compared to a DOX-Tet mixture and a three-fold increase compared to DOX-Tet NPs alone. When modified with macrophage membranes, these NPs enhance tumor targeting and cell uptake, thereby significantly reducing cancer cell viability. In animal studies, MM@DOX-Tet NPs outperformed single and conventional therapies, efficiently targeted tumors, and suppressed tumor growth. Furthermore, dual-layer encapsulation prevents drug leakage and increases drug accumulation at the tumor sites. Our study introduces MM@DOX-Tet NPs as a potential nano-drug system for overcoming MDR during breast cancer treatment.