PURPOSE: Platinum-based therapies are the first line treatments for most types of cancer including ovarian cancer. However, their use is associated with dose-limiting toxicities and resistance. We report initial translational studies of a theranostic nanoemulsion loaded with a cisplatin derivative, myrisplatin and pro-apoptotic agent, C6-ceramide. METHODS: The surface of the nanoemulsion is annotated with an endothelial growth factor receptor (EGFR) binding peptide to improve targeting ability and gadolinium to provide diagnostic capability for image-guided therapy of EGFR overexpressing ovarian cancers. A high shear microfludization process was employed to produce the formulation with particle size below 150 nm. RESULTS: Pharmacokinetic study showed a prolonged blood platinum and gadolinium levels with nanoemulsions in nu/nu mice. The theranostic nanoemulsions also exhibited less toxicity and enhanced the survival time of mice as compared to an equivalent cisplatin treatment. CONCLUSIONS: Magnetic resonance imaging (MRI) studies indicate the theranostic nanoemulsions were effective contrast agents and could be used to track accumulation in a tumor. The MRI study additionally indicate that significantly more EGFR-targeted theranostic nanoemulsion accumulated in a tumor than non-targeted nanoemulsuion providing the feasibility of using a targeted theranostic agent in conjunction with MRI to image disease loci and quantify the disease progression.
PURPOSE:Platinum-based therapies are the first line treatments for most types of cancer including ovarian cancer. However, their use is associated with dose-limiting toxicities and resistance. We report initial translational studies of a theranostic nanoemulsion loaded with a cisplatin derivative, myrisplatin and pro-apoptotic agent, C6-ceramide. METHODS: The surface of the nanoemulsion is annotated with an endothelial growth factor receptor (EGFR) binding peptide to improve targeting ability and gadolinium to provide diagnostic capability for image-guided therapy of EGFR overexpressing ovarian cancers. A high shear microfludization process was employed to produce the formulation with particle size below 150 nm. RESULTS: Pharmacokinetic study showed a prolonged blood platinum and gadolinium levels with nanoemulsions in nu/nu mice. The theranostic nanoemulsions also exhibited less toxicity and enhanced the survival time of mice as compared to an equivalent cisplatin treatment. CONCLUSIONS: Magnetic resonance imaging (MRI) studies indicate the theranostic nanoemulsions were effective contrast agents and could be used to track accumulation in a tumor. The MRI study additionally indicate that significantly more EGFR-targeted theranostic nanoemulsion accumulated in a tumor than non-targeted nanoemulsuion providing the feasibility of using a targeted theranostic agent in conjunction with MRI to image disease loci and quantify the disease progression.
Authors: Hardeep S Oberoi; Natalia V Nukolova; Alexander V Kabanov; Tatiana K Bronich Journal: Adv Drug Deliv Rev Date: 2013-10-08 Impact factor: 15.470
Authors: Abhimanyu S Paraskar; Shivani Soni; Kenneth T Chin; Padmaparna Chaudhuri; Katherine W Muto; Julia Berkowitz; Michael W Handlogten; Nathan J Alves; Basar Bilgicer; Daniela M Dinulescu; Raghunath A Mashelkar; Shiladitya Sengupta Journal: Proc Natl Acad Sci U S A Date: 2010-06-23 Impact factor: 11.205
Authors: Srinivas Ganta; Amit Singh; Yashesh Rawal; Joseph Cacaccio; Niravkumar R Patel; Praveen Kulkarni; Craig F Ferris; Mansoor M Amiji; Timothy P Coleman Journal: Drug Deliv Date: 2014-06-05 Impact factor: 6.419
Authors: William C Zamboni; Anne C Gervais; Merrill J Egorin; Jan H M Schellens; Deborah R Hamburger; Brian J Delauter; Amy Grim; Eleanor G Zuhowski; Erin Joseph; Dick Pluim; Douglas M Potter; Julie L Eiseman Journal: Clin Cancer Res Date: 2002-09 Impact factor: 12.531
Authors: Srinivas Ganta; Amit Singh; Niravkumar R Patel; Joseph Cacaccio; Yashesh H Rawal; Barbara J Davis; Mansoor M Amiji; Timothy P Coleman Journal: Pharm Res Date: 2014-03-19 Impact factor: 4.200
Authors: Niravkumar R Patel; Aleksandr Piroyan; Srinivas Ganta; Allison B Morse; Katie M Candiloro; April L Solon; Abbegail H Nack; Corin A Galati; Collete Bora; Marisa A Maglaty; Shane W O'Brien; Samuel Litwin; Barbara Davis; Denise C Connolly; Timothy P Coleman Journal: Cancer Biol Ther Date: 2018-05-08 Impact factor: 4.742