Abstract 384: Combination bioactive nanocarriers/anticancer agents for cancer therapy

Abstract

Abstract Purpose: Olive oil has been reported to play a beneficial role in cancer prevention and treatment. Currently, studies published on the anticancer effects of olive oil and oleic acid, one of the main components of olive oil, have been limited to in vitro cell studies or to simple trophology following oral administration in vivo. The effects of these natural compounds on cancer cells/tissues after parenteral delivery are largely unknown, and deserve investigation. Meanwhile, olive oil can also serve as a nanoemulsion, which can encapsulate drug molecules and be used as a drug carrier. Therefore, the development of bioactive nanocarriers that, ideally, would also have synergistic anticancer activity with cargo drugs, will introduce a new concept of drug carriers, which would have clinical significance for cancer therapy. Concept: Oleic acid, one of the main components of olive oil, was found to enhance the effectiveness of vinorelbine, a semi-synthetic vinca alkaloid, against various breast and prostate cancer cell lines. Oleic acid was found to dramatically reduce cellular levels of the receptor tyrosine kinase ErbB2, produced by the breast cancer oncogene Her-2/neu. Olive oil also contains at least 30 phenolic compounds, which are strong antioxidants and radical scavengers. If a cargo drug would have a synergistic effect with the components of olive oil and is then encapsulated into the olive oil nanoemulsion, the efficacy is expected to be stronger than that of conventional nanocarrier-based agents. If successful, this could go beyond the conventional concept of nanocarriers, i.e., an inert substance would no long be a prerequisite for drug carriers. Methods: In this study, olive oil was used as a drug carrier, and vinblastine (VIN) was used as an anticancer agent. Olive oil nanoemulsions were prepared using a sonication method, and the size distribution and VIN content of the nanoemulsions were characterized with dynamic light scattering and a spectrophotometer, respectively. Orthotopic xenograft tumor models were grown in female SCID mice by injecting human breast carcinoma MCF-7 cells or SK-BR-3 cells into the mammary fat pad of the animal. Animals received intravenous injection of (i) saline, (ii) vinblastine sulfate (5 mg/kg), (iii) olive oil nanoemulsions, or (iv) VIN-loaded olive oil nanoemulsions at days 1, 4, and 7. Tumor volumes and body weights were monitored twice a week, up to 30 days. Results/Discussion: The hydrodynamic size of olive oil nanoemulsions was 6 nm. Although vinblastine sulfate dramatically reduced the tumor volume, the drug led to lethal toxicity (6 of 6 mice). The olive oil nanoemulsion alone did not affect the tumor growth of MCF-7 xenografts. Studies of the anticancer activity of VIN-loaded olive oil nanoemulsion, an anticancer activity using SK-BR-3 xenografts, and the biodistribution of olive oil nanoemulsions are currently under investigation. Acknowledgment: Supported by The Nagai Foundation, Tokyo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 384. doi:10.1158/1538-7445.AM2011-384