title: Tumor-targeted responsive nanoparticle-based systems for magnetic resonance imaging and therapy.
abstract: OBJECTIVE
  Design and synthesis of a tumor responsive nanoparticle-based system for imaging and treatment of various cancers.
  
  
  METHODS
  Manganese oxide nanoparticles (Mn3O4 NPs) were synthesized and modified with LHRH targeting peptide or anti-melanoma antibodies (cancer targeting moieties) and a MMP2 cleavable peptide (a possible chemotactic factor). Nanostructured lipid carriers (NLCs) were used to entrap the BRAF inhibitor, vemurafenib, and enhance cytotoxicity of the drug. Size distribution, stability, drug entrapment, cytotoxicity and genotoxicity of synthesized nanoparticles were studied in vitro. Enhancement of MRI signal by nanoparticles and their body distribution were examined in vivo on mouse models of melanoma, ovarian and lung cancers.
  
  
  RESULTS
  Uniform, stable cancer-targeted nanoparticles (PEGylated water-soluble Mn3O4 NPs and NLCs) were synthesized. No signs of cyto-,genotoxicity and DNA damage were detected for nanoparticles that do not contain an anticancer drug. Entrapment of vemurafenib into nanoparticles significantly enhanced drug toxicity in cancer cells with targeted V600E mutation. The developed nanoparticles containing LHRH and MMP2 peptides showed preferential accumulation in primary and metastatic tumors increasing the MRI signal in mice with melanoma, lung and ovarian cancers.
  
  
  CONCLUSIONS
  The proposed nanoparticle-based systems provide the foundation for building an integrated MRI diagnostic and therapeutic approach for various types of cancer.
authors.affiliation: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, New Jersey, 08854, USA.
authors.forename: Ronak
authors.initials: R
authors.lastname: Savla
authors.forename: Olga B
authors.initials: OB
authors.lastname: Garbuzenko
authors.forename: Suzie
authors.initials: S
authors.lastname: Chen
authors.forename: Lorna
authors.initials: L
authors.lastname: Rodriguez-Rodriguez
authors.forename: Tamara
authors.initials: T
authors.lastname: Minko
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D001672:Biocompatible Materials; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D017895:Manganese Compounds / Q000737:chemistry; D008545:Melanoma / Q000175:diagnosis / Q000188:drug therapy; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000188:drug therapy; D010087:Oxides / Q000737:chemistry; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use; D014018:Tissue Distribution; D000077484:Vemurafenib
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D003287:Contrast Media; D004337:Drug Carriers; D007211:Indoles; D017895:Manganese Compounds; D010087:Oxides; D013449:Sulfonamides; D000077484:Vemurafenib; C027424:manganese oxide