Inhibiting metastatic breast cancer cell migration via the synergy of targeted, pH-triggered siRNA delivery and chemokine axis blockade.
Because breast cancer patient survival inversely correlates with metastasis, we engineered vehicles to inhibit both the C-X-C chemokine receptor type 4 (CXCR4) and lipocalin-2 (Lcn2) mediated migratory pathways. pH-responsive liposomes were designed to protect and trigger the release of Lcn2 siRNA. Liposomes were modified with anti-CXCR4 antibodies to target metastatic breast cancer (MBC) cells and block migration along the CXCR4-CXCL12 axis. This synergistic approach--coupling the CXCR4 axis blockade with Lcn2 silencing--significantly reduced migration in triple-negative human breast cancer cells (88% for MDA-MB-436 and 92% for MDA-MB-231). The results suggested that drug delivery vehicles engineered to attack multiple migratory pathways may effectively slow progression of MBC.
Department of Biomedical Engineering, The City College of New York , 160 Convent Avenue, New York, New York 10031, United States.
Peng
P
Guo
Jin-Oh
JO
You
Jiang
J
Yang
Di
D
Jia
Marsha A
MA
Moses
Debra T
DT
Auguste
D000209:Acute-Phase Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D016503:Drug Delivery Systems; D004357:Drug Synergism; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006863:Hydrogen-Ion Concentration; D000071068:Lipocalin-2; D054834:Lipocalins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008081:Liposomes; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D064726:Triple Negative Breast Neoplasms / Q000556:secondary / Q000628:therapy*; D014407:Tumor Cells, Cultured
D000209:Acute-Phase Proteins; D000911:Antibodies, Monoclonal; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D008081:Liposomes; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4