International Journal of Nanomedicine (Dec 2020)
Enhanced Antitumor Efficacy of Macrophage-Mediated Egg Yolk Lipid-Derived Delivery System Against Breast Cancer
Abstract
Yanguan Lv,1,* Yali Jun,2,* Zhuang Tang,2,3,* Xiang Li,2 Mingyue Tao,2,4 Zhengwei Zhang,5 Lu Liu,5 Su’An Sun,5 Qilong Wang,2 Chao Luo,2 Li Zhang2 1Department of Clinical Medical Laboratory, Huai’an Maternity and Child Healthcare Hospital Affiliated to Yangzhou University Medical Academy, Huai’an 223002, People’s Republic of China; 2Department of Central Laboratory, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an 223300, People’s Republic of China; 3School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau, 999078, People’s Republic of China; 4Department of Clinical Oncology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an 223300, People’s Republic of China; 5Department of Pathology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an 223300, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Zhang; Chao LuoDepartment of Central Laboratory, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an 223300, People’s Republic of ChinaTel +8615861710452Email [email protected]; [email protected]: 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.Keywords: macrophage, drug delivery, target therapy, egg yolk lipid-derived nanovector, breast cancer