ICAM-1-Targeted, Lcn2 siRNA-Encapsulating Liposomes are Potent Anti-angiogenic Agents for Triple Negative Breast Cancer.

摘要: Lipocalin 2 (Lcn2) is a promising therapeutic target as well potential diagnostic biomarker for breast cancer. It has been previously shown to promote cancer progression by inducing the epithelial mesenchymal transition in cells enhancing angiogenesis. Lcn2 levels urine and tissue samples of patients also correlated with status poor patient prognosis. In this study, we have engineered novel liposomal small interfering RNA (siRNA) delivery system triple negative (TNBC) via recently identified molecular target, intercellular adhesion molecule-1 (ICAM-1). This ICAM-1-targeted, siRNA- encapsulating liposome (ICAM-Lcn2-LP) binds human TNBC MDA-MB-231cells significantly stronger than non-neoplastic MCF-10A cells. Efficient knockdown ICAM-Lcn2-LPs led significant reduction production vascular endothelial growth factor (VEGF) from MDA-MB-231 cells, which, turn, reduced angiogenesis both vitro vivo. Angiogenesis (neovascularization) requirement solid tumor progression, its inhibition an important strategy cancers. Our results indicate that tumor-specific such TNBC-targeted, anti-angiogenic approach developed here, may be clinically useful inhibiting progression.