LAUSR

Objectives: Paclitaxel (Ptxl) is currently the most common first-line therapeutic option for breast cancer (BrCa). However, adverse side effects and problems associated with chemo-resistance, limits its use in clinical settings. Nanoparticle mediated delivery can improve Ptxl delivery and its activity at the tumor site, and considered to be an attractive strategy for BrCa therapy. Therefore, we aim to generate a novel Ptx medical nanoparticle formulation (PMNPs) using a polyphenol as a carrier, and evaluate its efficacy against BrCa cells. Methods: Physico-chemical characterization of this PMNPs was performed using TEM, DLS, FT-IR, TGA, X-RD, and SAXS methods. Its internalization and cellular availability was examined using HPLC method. Cell proliferation and colony formation assays were utilized to evaluate therapeutic efficacy of this unique nanoformulation in clinically relevant cell line models (MCF7 and MDA-MB-231). Additionally, molecular effects of this formulation on apoptosis, anti-apoptosis, and drug resistant associated proteins were evaluated using immunoblotting assays. A tubulin stabilization study was performed using confocal immunofluorescence microscopy analysis. Results: The PMNPs formulation showed optimal particle size and zeta potential, which can be efficiently internalized in BrCa cells. PMNPs exhibited potent anti-cancer efficacy via induction of the expression of apoptosis associated proteins (Bax and Bad, cleaved PARP, and caspase 3) and downregulation of anti-apoptotic proteins (Bcl-2 and Bcl-xL) in BrCa ell lines. Further, the expression of chemoresistance-associated proteins were also decreased with the treatment of PMNPs. Conclusion: PMNPs formulation can efficiently be internalized in BrCa cells and induce enhanced therapeutic potential of Ptxl. Development of a targeted drug delivery system would not only reduce the dose of paclitaxel required to kill cancer cells but also minimize long-term paclitaxel associated systemic toxicity and drug-resistance. Citation Format: Pallabita Chowdhury, Sumeet S. Chauhan, Prashanth K. Nagesh, Elham Hatami, Bilal B. Hafeez, Sheema Khan, Meena Jaggi, Murali M. Yallapu. Novel paclitaxel medical nanoparticle formulation for breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4658.