Abstract 5531: Combination drug delivery using PBM nanoparticle to improve prostate cancer therapy

Abstract

Abstract Docetaxel is the standard first-line chemotherapy for advanced prostate cancer (PCa). The key challenges in this treatment option are dose-limiting toxicities, acquired resistance, and lack of tumor cell specificity. Adjuvants and docetaxel encapsulation have been proposed to mitigate many of these hindrances. The proposed study evaluated a novel method for targeted delivery of resveratrol alone or in combination with docetaxel at desired rates. We described a proprietary planetary ball milling approach (PBM) that uses a natural polysaccharide (starch; FDA approved) to create a drug-polysaccharide nanoparticle as a core that is subsequently coated with novel folate-conjugated poly (ϵ-caprolactone) / poly (ethylene glycol) co-polymer, which allows binding to high affinity folate receptors present on PCa cells. The resulting PBM nanoparticles were shown to be rapidly internalized and induce significant cancer cell apoptosis at lower doses, than compared to unformulated resveratrol and/or docetaxel. Importantly, negative controls showed that PBM nanoparticles without resveratrol or docetaxel had no toxic effects on PCa cells. Furthermore, our data also suggests that resveratrol potently synergizes with docetaxel to inhibit proliferation and induce 60% cell death in PCa cell lines at concentrations lower than the IC50. Since docetaxel is associated with various debilitating toxicities, a synergistic combination of resveratrol-docetaxel with targeted delivery to tumor cells could provide a more potent therapeutic effect at lower drug concentrations and improve therapeutic index. Citation Format: Rajesh Singh, Shailesh Singh, Guru P. Sonpavde, James W. Lillard. Combination drug delivery using PBM nanoparticle to improve prostate cancer therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5531. doi:10.1158/1538-7445.AM2015-5531