Theranostics 2016; 6(1):1-13. doi:10.7150/thno.12167 This issue
1. Department of Biomedical Engineering, The City College of New York, 160 Convent Avenue, New York, NY 10031, United States
2. Vascular Biology Program, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, United States
3. Department of Surgery, Harvard Medical School and Boston Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, United States
†These authors contributed equally to this work, and are co-first authors.
‡These authors contributed equally to this work, and are co-last authors.
Lipocalin 2 (Lcn2) is a promising therapeutic target as well as a potential diagnostic biomarker for breast cancer. It has been previously shown to promote breast cancer progression by inducing the epithelial to mesenchymal transition in breast cancer cells as well as by enhancing angiogenesis. Lcn2 levels in urine and tissue samples of breast cancer patients has also been correlated with breast cancer status and poor patient prognosis. In this study, we have engineered a novel liposomal small interfering RNA (siRNA) delivery system to target triple negative breast cancer (TNBC) via a recently identified molecular target, intercellular adhesion molecule-1 (ICAM-1). This ICAM-1-targeted, Lcn2 siRNA- encapsulating liposome (ICAM-Lcn2-LP) binds human TNBC MDA-MB-231cells significantly stronger than non-neoplastic MCF-10A cells. Efficient Lcn2 knockdown by ICAM-Lcn2-LPs led to a significant reduction in the production of vascular endothelial growth factor (VEGF) from MDA-MB-231 cells, which, in turn, led to reduced angiogenesis both in vitro and in vivo. Angiogenesis (neovascularization) is a requirement for solid tumor growth and progression, and its inhibition is an important therapeutic strategy for human cancers. Our results indicate that a tumor-specific strategy such as the TNBC-targeted, anti-angiogenic therapeutic approach developed here, may be clinically useful in inhibiting TNBC progression.
Keywords: ICAM-1, Lipocalin-2, liposomal siRNA, triple-negative breast cancer, angiogenesis