title: Curcumin-loaded magnetic nanoparticles for breast cancer therapeutics and imaging applications.
abstract: BACKGROUND
  The next generation magnetic nanoparticles (MNPs) with theranostic applications have attracted significant attention and will greatly improve nanomedicine in cancer therapeutics. Such novel MNP formulations must have ultra-low particle size, high inherent magnetic properties, effective imaging, drug targeting, and drug delivery properties. To achieve these characteristic properties, a curcumin-loaded MNP (MNP-CUR) formulation was developed.
  
  
  METHODS
  MNPs were prepared by chemical precipitation method and loaded with curcumin (CUR) using diffusion method. The physicochemical properties of MNP-CUR were characterized using dynamic light scattering, transmission electron microscopy, and spectroscopy. The internalization of MNP-CUR was achieved after 6 hours incubation with MDA-MB-231 breast cancer cells. The anticancer potential was evaluated by a tetrazolium-based dye and colony formation assays. Further, to prove MNP-CUR results in superior therapeutic effects over CUR, the mitochondrial membrane potential integrity and reactive oxygen species generation were determined. Magnetic resonance imaging capability and magnetic targeting property were also evaluated.
  
  
  RESULTS
  MNP-CUR exhibited individual particle grain size of ~9 nm and hydrodynamic average aggregative particle size of ~123 nm. Internalized MNP-CUR showed a preferential uptake in MDA-MB-231 cells in a concentration-dependent manner and demonstrated accumulation throughout the cell, which indicates that particles are not attached on the cell surface but internalized through endocytosis. MNP-CUR displayed strong anticancer properties compared to free CUR. MNP-CUR also amplified loss of potential integrity and generation of reactive oxygen species upon treatment compared to free CUR. Furthermore, MNP-CUR exhibited superior magnetic resonance imaging characteristics and significantly increased the targeting capability of CUR.
  
  
  CONCLUSIONS
  MNP-CUR exhibits potent anticancer activity along with imaging and magnetic targeting capabilities. This approach can be extended to preclinical and clinical use and may have importance in cancer treatment and cancer imaging in the future. Further, if these nanoparticles can functionalize with antibody/ligands, they will serve as novel platforms for multiple biomedical applications.
authors.affiliation: Cancer Biology Research Center, Sanford Research/University of South Dakota, Sioux Falls, SD 57104-0589, USA.
authors.forename: Murali M
authors.initials: MM
authors.lastname: Yallapu
authors.forename: Shadi F
authors.initials: SF
authors.lastname: Othman
authors.forename: Evan T
authors.initials: ET
authors.lastname: Curtis
authors.forename: Nichole A
authors.initials: NA
authors.lastname: Bauer
authors.forename: Neeraj
authors.initials: N
authors.lastname: Chauhan
authors.forename: Deepak
authors.initials: D
authors.lastname: Kumar
authors.forename: Meena
authors.initials: M
authors.lastname: Jaggi
authors.forename: Subhash C
authors.initials: SC
authors.lastname: Chauhan
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D003474:Curcumin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D050997:Nanomedicine; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D058185:Magnetite Nanoparticles; D017382:Reactive Oxygen Species; D003474:Curcumin