Development of Magnetic Nanovectors for Treatment and Imaging of Breast Cancer Metastasis to the Brain

Abstract : Treating breast cancer that has metastasized to the central nervous system remains a formidable challenge due to, 1) its high malignancy, 2) the difficulty in differentiating between tumor and healthy brain tissue, 3) the sensitivity of normal brain tissue to the toxicities of current therapies, 4) intrinsic cellular resistance of BMBC cells to chemotherapeutic drugs, and 5) the blood-brain barrier s (BBB) ability to prevent the passage of extrinsic substances such as drugs and contrast agents. Our aim is to develop magnetic contrast agents and targeted siRNA therapies capable of overcoming the blood brain barrier and to aid in both the diagnosis and treatment brain metastatic breast cancer. Magnetic nanoparticles with high susceptibility have been developed. These nanoparticles have been characterized to be monodispersed are working to engineer a nanovector that will aid in addressing the major challenges associated with the diagnosis and treatment of BMBC. The major components of the nanovector include a Fe3O4 superparamagnetic nanoparticle (NP) core and a shell comprised of a copolymer of polyethylene glycol (PEG)-grafted chitosan (C)-polyethyleneimine (P), or CP. The tumor targeting peptide, chlorotoxin (CTX), and siRNA (designed to knockdown the pro metastasis gene MENA) also are conjugated to the NP polymer overcoat.