title: Development of EGFR-targeted nanoemulsion for imaging and novel platinum therapy of ovarian cancer.
abstract: OBJECTIVE
  Platinum-based chemotherapy is the treatment of choice for malignant epithelial ovarian cancers, but generalized toxicity and platinum resistance limits its use. Theranostic nanoemulsion with a novel platinum prodrug, myrisplatin, and the pro-apoptotic agent, C6-ceramide, were designed to overcome these limitations.
  
  
  METHODS
  The nanoemulsions, including ones with an EGFR binding peptide and gadolinium, were made using generally regarded as safe grade excipients and a high shear microfluidization process. Efficacy was evaluated in ovarian cancer cells, SKOV3, A2780 and A2780CP.
  
  
  RESULTS
  The nanoemulsion with particle size <150 nm were stable in plasma and parenteral fluids for 24 h. Ovarian cancer cells in vitro efficiently took up the non-targeted and EGFR-targeted nanoemulsions; improved cytotoxicity was observed for the these nanoemulsions with the latter showing a 50-fold drop in the IC50 in SKOV3 cells as compared to cisplatin alone. The addition of gadolinium did not affect cell viability in vitro, but showed relaxation times comparable to Magnevist(®).
  
  
  CONCLUSIONS
  The myrisplatin/C6-ceramide nanoemulsion synergistically enhanced in vitro cytotoxicity. An EGFR binding peptide addition further increased in vitro cytotoxicity in EGFR positive cancer cells. The diagnostic version showed MR imaging similar to the clinically relevant Magnevist® and may be suitable as a theranostic for ovarian cancer.
authors.affiliation: Nemucore Medical Innovations, Inc., Worcester, Massachusetts, 01608, USA.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ganta
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
authors.forename: Niravkumar R
authors.initials: NR
authors.lastname: Patel
authors.forename: Joseph
authors.initials: J
authors.lastname: Cacaccio
authors.forename: Yashesh H
authors.initials: YH
authors.lastname: Rawal
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Davis
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Amiji
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Coleman
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002518:Ceramides / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D004655:Emulsions / Q000737:chemistry / Q000378:metabolism; D005260:Female; D005682:Gadolinium / Q000737:chemistry / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008969:Molecular Sequence Data; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D010053:Ovary / Q000187:drug effects / Q000473:pathology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002518:Ceramides; D004337:Drug Carriers; D004655:Emulsions; D009944:Organoplatinum Compounds; D010455:Peptides; C485184:enhanced green fluorescent protein; C000606482:myrisplatin; C101954:N-caproylsphingosine; D049452:Green Fluorescent Proteins; D005682:Gadolinium