EGFR Targeted Theranostic Nanoemulsion for Image-Guided Ovarian Cancer Therapy.
OBJECTIVE
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.
Nemucore Medical Innovations, Inc., Worcester, Massachusetts, 01608, USA.
Srinivas
S
Ganta
Amit
A
Singh
Praveen
P
Kulkarni
Amanda W
AW
Keeler
Aleksandr
A
Piroyan
Rupa R
RR
Sawant
Niravkumar R
NR
Patel
Barbara
B
Davis
Craig
C
Ferris
Sara
S
O'Neal
William
W
Zamboni
Mansoor M
MM
Amiji
Timothy P
TP
Coleman
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001792:Blood Platelets / Q000378:metabolism; D002518:Ceramides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D066246:ErbB Receptors / Q000187:drug effects*; D005260:Female; D005682:Gadolinium / Q000378:metabolism; D051379:Mice; D044085:Microfluidics; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010316:Particle Size; D016019:Survival Analysis; D000068936:Theranostic Nanomedicine / Q000379:methods*; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D002518:Ceramides; D009944:Organoplatinum Compounds; C000606482:myrisplatin; C101954:N-caproylsphingosine; D005682:Gadolinium; D066246:ErbB Receptors