Abstract 2208: Novel nanoparticle formulation of Plumbagin for pancreatic cancer treatment

Pancreatic cancer (PanCa) is one of the most fatal of all cancers and is ranked as the fourth most common cause of cancer related deaths among both men and women in the US. The management of PanCa, is exceptionally difficult due to the extremely poor response to available therapeutic modalities. Highly desmoplastic microenvironment in pancreatic tumor causes suboptimal drug delivery and increases chemo-resistance. Plumbagin (PL), a naturally occurring napthoquinone derived from the root of Plumbago zeylanica L., has showed potent cancer preventive and therapeutic activity against variety of cancers. However, the clinical translation of PL has been significantly hampered due to its toxicity and suboptimal bioavailability. To address these clinically relevant issues, we have developed and characterized a novel PL-loaded magnetic nanoparticle (MNP-PL) formulation. This MNP-PL formulation was prepared using Magnetic nanoparticles (MNPs) composed of an iron oxide core which has distinct advantages in i) bio/hemo-compatibility, ii) biodegradation, iii) higher drug loading capacity and iv) improved bioavailability. Our novel MNP-PL formulation provided average size of 125 nm in dynamic light scattering (DLS) and exhibited -9.42 to -10.79 mV zeta potential with an outstanding PL loading efficiency. We have evaluated anti-cancer potential of MNP-PL formulation in human PanCa cells (HPAF-II, AsPc1 and Panc-1). We first performed MTS and colony formation assays to determine the effects of free PL and MNP-PL formulation on growth of PanCa cells. In this experiment, cells were treated with various concentrations of free PL (1-15 μM) or MNP-PL (1-15 μM) for 24 hrs. Results exhibited efficient internalization of the MNP-PL formulation in a dose-dependent manner. As a result, the MNP-PL formulation showed four fold dose advantage over free PL. IC50 of free PL was recorded 10 μM which was significantly reduced to 2.5 μM in MNP-PL. MNP-PL also showed four fold inhibition in colony formation compared to free PL. MNP-PL treatment more efficiently inhibited oncogenic CXCL12/CXCR4 signaling pathway in both PanCa and patient derived stromal fibroblast cells. MNP-PL treatment also showed decreased expression of CXCR4 protein levels in PanCa cells. Moreover, MNP-PL treatment inhibited stromal derived factor 1 (SDF-1)/CXCL12 expression in stromal fibroblasts. These results suggest that our novel MNP-PL formulation has more anti-cancer potential than free PL against PanCa. In conclusion, MNP-PL formulation may reduce the toxicity and improve the bioavailability of free PL and could be used for the treatment of PanCa. Citation Format: Bilal B. Hafeez, Vivek K. Kashyap, Vijayakumar N. Boya, Aditya Ganju, Mohammad Sikander, Murali M. Yallapu, Meena Jaggi, Subhash C. Chauhan. Novel nanoparticle formulation of Plumbagin for pancreatic cancer treatment. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2208.