Targeting Survivin: A SPION-Based Approach to Cancer Diagnostics and Therapy

Despeaux, Emily ;   Talbott, Siera ;   Gannett, Peter ;   Pisane, Kelly ;   Seehra, Mohindar ;   Carroll, R. Lloyd

Magnetic nanoparticles, including superparamagnetic iron oxide nanoparticles (SPION), have the potential to significantly improve the diagnosis and treatment of cancer. Insufficient imaging sensitivity makes it difficult to delineate the extent a patient?s disease, while treatments are limited by the inability of chemotherapeutic agents to act selectively on malignant cells. SPION-based agents have received FDA approval for use as both iron replacement therapy in patients with kidney disease and MRI contrast agents. Improved specificity for both localization and therapeutic action can be achieved through conjugation with a disease-specific ligand. Conjugation with an antisense oligonucleotide (ASO) targeting survivin, an anti-apoptotic protein over-expressed in cancer cells, provides a therapeutic target unique to malignant cells. We have synthesized seven nanometer SPIONs coated with a biocompatible polymer and conjugated to a survivin ASO. Our SPIONs enter A549 lung adenocarcinoma cells and initial toxicity studies showed that the viability of A549 cells incubated with ASO coupled SPIONs decreased in a dose-dependent manner, while SPIONs coupled to an inert control sequence had no effect on cell viability.