Enhanced Antitumor Efficacy of Macrophage-Mediated Egg Yolk Lipid-Derived Delivery System Against Breast Cancer.

ABSTRACT

BACKGROUND: Chemotherapy is the primary treatment for most cancers apart from surgery. However, the use of chemotherapeutic drugs is limited by side effects and restricted accumulation in tumors because of unique tumor microenvironments. Macrophages have excellent drug delivery potential owing to their chemotaxis and can home in on tumors. MATERIALS AND METHODS: We developed an effective drug-delivery system for doxorubicin using macrophages. Doxorubicin-loaded egg yolk lipid-derived nanovectors (EYLNs-Dox) were prepared, EYLNs-Dox-loaded macrophages (Mac/EYLNs-Dox) were developed and their tumor penetration and anti-cancer activity against 4T1 cells were analyzed. The biodistribution and anti-4T1 breast cancer activities were determined using 4T1 subcutaneous and lung metastasis models. RESULTS: EYLNs-Dox was successfully internalized into macrophages without affecting their viability and was less toxic than Dox. Mac/EYLNs-Dox penetrated the 4T1 tumor spheroids more efficiently and was more effective in inhibiting tumors in vitro. Macrophages significantly enhanced the distribution of EYLNs vectors in both inflammatory and tumor sites, playing a more effective role in the inhibition of tumors. CONCLUSION: EYLNs-Dox can be effectively delivered using macrophages and Mac/EYLNs-Dox might be a promising targeted delivery system for breast cancer.