Abstract
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.
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Abbreviations
- DNA:
-
Deoxyribonucleic acid
- EGFR:
-
Endothelial growth factor receptor
- g:
-
Grams
- Gd:
-
Gadolinium
- hrs/h:
-
Hours
- kg:
-
Kilograms
- mg:
-
Milligrams
- min:
-
Minutes
- mm:
-
Millimeters
- mmoles:
-
Millimoles
- msec:
-
Milliseconds
- mV:
-
Millivolts
- ng:
-
Nanograms
- nm:
-
Nanometers
- psi:
-
Pounds per square inch
- Pt:
-
Platinum
- rpm:
-
Revolutions per minute
- w/v :
-
Weight/volume
- μL:
-
Microliters
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ACKNOWLEDGMENTS AND DISCLOSURES
This study was supported by the NIH grants (R43 CA144591 and U54 CA151881). The Authors would like to thank Susan Riley Keyes, Allison Morse, Samantha Orosz, Laurie Cote, Phil Heisler and Keri Forbringer for their insightful discussion of the findings and assistance with development of this manuscript.
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Ganta, S., Singh, A., Kulkarni, P. et al. EGFR Targeted Theranostic Nanoemulsion for Image-Guided Ovarian Cancer Therapy. Pharm Res 32, 2753–2763 (2015). https://doi.org/10.1007/s11095-015-1660-z
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DOI: https://doi.org/10.1007/s11095-015-1660-z